Antibodies for cancer research

The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. Alternatively referred to as a breast cancer resistance protein, this protein functions as a xenobiotic transporter which may play a major role in multi-drug resistance. It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure. Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue.Tissue specificity: Highly expressed in placenta. Low expression in small intestine, liver and colon.

The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. Alternatively referred to as a breast cancer resistance protein, this protein functions as a xenobiotic transporter which may play a major role in multi-drug resistance. It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure. Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue.Tissue specificity: Highly expressed in placenta. Low expression in small intestine, liver and colon.

ABL2(ARG, Abelson-related gene) is a cytoplasmic tyrosine kinase which is closely related to but distinct from ABL1. The similarity of the proteins includes the tyrosine kinase domains and extends amino-terminal to include the SH2 and SH3 domains. ABL2 is expressed in both normal and tumor cells. The ABL2 gene product is expressed as two variants bearing different amino termini, both approximately 12-kb in length. c-Abl shows both cytoplasmic and nuclear localization，c-Abl is involved in two different chromosomal translocations present in human leukemias, which generate Bcr-Abl and TEL-Abl.

The poly Q polymorphism in (amplified in breast cancer) gene is usually assessed by fragment length analysis which does not reveal the actual sequence variation. The purpose of this study is to investigate the sequence variation of poly Q encoding region in breast cancer cell lines at single molecule level, and to determine if the sequence variation is related to AIB1 gene amplification.

Akt2 (also designated protein kinase B beta or v-akt murine thymoma viral oncogene homolog 2 ), with 481-amino acid protein (about 53kDa), belongs to the AKT serine/threonine protein kinase family, which also includes Akt1 and Akt3. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. Among the members of AKT family, Akt2 is associated with the development of human cancers. Akt2 inhibits cisplatin-induced JNK/p38 and Bax activation through phosphorylation of ASK1 and thus, plays an important role in chemoresistance. Further, Akt2 plays a specific role in muscle differentiation.

Akt3 (also designated protein kinase B gamma or v-akt murine thymoma viral oncogene homolog 3)，with 479-amino acid protein (about 53kDa), belongs to the AKT serine/threonine protein kinase family, which also includes Akt1 and Akt2. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake.Akt3 is not required for the maintenance of normal carbohydrate metabolism but is essential for the attainment of normal organ size. Identifying Akt3 as a selective target in melanoma cells also provides new therapeutic opportunities for patients in the advanced stages of this disease.

AMACR (alpha-methylacyl-CoA racemase) has been recently described as prostate cancer-specific gene that encodes a protein involved in the beta-oxidation of branched chain fatty acids. Expression of AMACR protein is found in prostatic adenocarcinoma but not in benign prostatic tissue. It stains premalignant lesions of prostate: high-grade prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia. AMACR can be used as a positive marker for PIN. Defects in AMACR are the cause of congenital bile acid synthesis defect type 4 (CBAS4); also known as cholestasis, intrahepatic, with defective conversion of trihydroxycoprostanic acid to cholic acid or trihydroxycoprostanic acid in bile. Clinical features include neonatal jaundice, intrahepatic cholestasis, bile duct deficiency and absence of cholic acid from bile.

The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder.Tissue specificity: Found in pancreas, kidney, skeletal muscle, liver, lung, placenta, brain, heart, spleen, thymus, testis, ovary, small intestine, colon and leukocytes.

Aurora A plays a role in cell cycle regulation during anaphase and/or telophase, in relation to the function of the centrosome/spindle pole region during chromosome segregation. Aurora A plays a key role during tumor development and progression and is overexpressed in many human cancers including breast, ovarian and colorectal. Aurora A is viewed as a potential target for anticancer drug treatment.Tissue specificity: Highly expressed in testis and weakly in skeletal muscle, thymus and spleen. Also highly expressed in colon, ovarian, prostate, neuroblastoma, breast and cervical cancer cell lines.

Beclin-1 participates in the regulation of autophagy and has an important role in development, tumorigenesis, and neurodegeneration (Zhong et al., 2009 (PubMed 19270693)).(supplied by OMIM) . Tissue specificity: Ubiquitous.

This gene is a member of the inhibitor of apoptosis (IAP) gene family, which encode negative regulatory proteins that prevent apoptotic cell death. IAP family members usually contain multiple baculovirus IAP repeat (BIR) domains, but this gene encodes proteins with only a single BIR domain. The encoded proteins also lack a C-terminus RING finger domain. Gene expression is high during fetal development and in most tumors, yet low in adult tissues. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

BRAF(V-raf murine sarcoma viral oncogene homolog B1 ) is the main  effectors recruited by GTP-bound Ras to activate the MEK-MAP kinase pathway. B-Raf contains three consensus Akt phosphorylationsites (Ser364, Ser428, and Thr439).B-Raf is a key regulatory molecule of the mitogen-activated protein kinase kinase (MEK),it has a long amino-terminal region,the region is essential for homo-dimerization of B-Raf and hetero-dimerization of B-Raf and c-Raf at the plasma membrane, followed by phosphorylation  of Thr118 in the amino-terminal  B-Raf-specific region.  Notably, in calcium ionophore-stimulated HeLa cells, B-Raf could propagate signals to MEK under the basal level of GTP-Ras. Expression of Raf-B is highly restricted with highestlevels in the cerebrum and testes and defects in braf are involved in a wide range of cancers.The BRAF gene mutation  is frequently detected in  papillary thyroid carcinoma,melanocytic nevi,primary cutaneous melanomas and colorectal cancers.

C-kit (CD117, 145kDa) functions as a tyrosine kinase receptor which becomes activated upon binding of its ligand SCF (stem-cell factor), the C-kit gene encodes the human homolog of the proto-oncogene c-kit. which was first identified as the cellular homolog of the feline sarcoma viral oncogene v-kit. KIT is a type 3 transmembrane receptor for MGF (mast cell growth factor). Mutations in KIT are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous lukemia, and piebaldism.

CA IX is a transmembrane protein and the only tumor-associated carbonic anhydrase isoenzyme known. It is expressed in all clear-cell renal cell carcinoma, but is not detected in normal kidney or most other normal tissues. It may be involved in cell proliferation and transformation. Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia. Tissue specificity: Expressed primarily in carcinoma cells lines. Expression is restricted to very few normal tissues and the most abundant expression is found in the epithelial cells of gastric mucosa.

The protein encoded by this gene is a regulatory protein involved in mitosis. The gene product complexes with p34(cdc2) to form the maturation-promoting factor (MPF). Two alternative transcripts have been found, a constitutively expressed transcript and a cell cycle-regulated transcript, that is expressed predominantly during G2/M phase. The different transcripts result from the use of alternate transcription initiation sites. (provided by RefSeq) It has higher expression in tumor tissues .

During each cell cycle cyclins undergo periodic accumulation and destruction. As key regulators of the cell cycle the cyclins control important transitions by acting as regulatory subunits of the Cdks. Early in the G1 phase of the cell cycle, cyclin D1 induction is followed by cyclin E induction. This sequential progression is marked early on in G1 by the activation of Cdk4 and in mid to late G1 by the activation of Cdk2 and the hyperphosphorylation of pRB. The final transition into S phase is thought to be dependent on the increased expression and association of cyclin E and Cdk2. In a recent study, Cyclin D1 regulates cellular metabolism, fat cell differentiation and cellular migration. Cyclin D1 is also involved in development and cancer. Cyclin D1 has also been linked to the development and progression of several cancers including breast, bladder, esophagus, and lung.

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activtiy is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. Several transcript variants encoding different isoforms have been found for this gene.

This gene encodes a pentaspan transmembrane glycoprotein. The protein localizes to membrane protrusions and is often expressed on adult stem cells, where it is thought to function in maintaining stem cell properties by suppressing differentiation. Mutations in this gene have been shown to result in retinitis pigmentosa and Stargardt disease. Expression of this gene is also associated with several types of cancer. This gene is expressed from at least five alternative promoters that are expressed in a tissue-dependent manner. Multiple transcript variants encoding different isoforms have been found for this gene.

Costimulatory B7 molecules (e.g., B7-1, or CD80; MIM 112203) signal through CD28 (MIM 186760) family molecules such as CD28, CTLA4 (MIM 123890), and ICOS (MIM 604558). May participate in the regulation of T-cell-mediated immune response. May play a protective role in tumor cells by inhibiting natural-killer mediated cell lysis as well as a role of marker for detection of neuroblastoma cells. May be involved in the development of acute and chronic transplant rejection and in the regulation of lymphocytic activity at mucosal surfaces. Could also play a key role in providing the placenta and fetus with a suitable immunological environment throughout pregnancy. Both isoform 1 and isoform 2 appear to be redundant in their ability to modulate CD4 T-cell responses. Isoform 2 is shown to enhance the induction of cytotoxic T-cells and selectively stimulates interferon gamma production in the presence of T-cell receptor signaling.

CD31, also known as platelet endothelial cell adhesion molecule 1 (PECAM1), is a type I integral membrane glycoprotein and a member of the immunoglobulin superfamily of cell surface receptors.It is constitutively expressed on the surface of endothelial cells, and concentrated at the junction between them. The antibody reacts with the murine form of the Platelet-Endothelial Cell Adhesion Molecule. The reactivity of the antibody is restricted to the isoform of the molecule that is selectively expressed by endothelial cells.The antigen is predominantly present at the lateral borders of endothelial cells as described for human PECAM-1.It is also weakly expressed on many peripheral lymphoid cells and platelets.CD31 has been used to measure angiogenesis in association with tumor recurrence. Other studies have also indicated that CD31 and CD34 can be used as markers for myeloid progenitor cells and recognize different subsets of myeloid leukemia infiltrates (granular sarcomas).

CD34 is a transmembrane glycoprotein with a molecular mass of approximately 110 kD that is selectively expressed on human hematopoietic progenitor cells, endothelial cells and some fibroblasts. It could act as a scaffold for the attachment of lineage specific glycans, allowing stem cells to bind to lectins expressed by stromal cells or other marrow components. CD34 is highly expressed on hematopoietic progenitors, as well as on endothelial cells. CD34 has been used to measure angiogenesis, which reportedly predicts tumor recurrence.

CD44, also known as IN, LHRMIC4, CDW44, HCELL. It is a cell-surface glycoprotein involved in cell-cell interactions, cell adhesion and migration. It is a receptor for hyaluronic acid (HA) and can also interact with other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). This protein participates in a wide variety of cellular functions including lymphocyte activation, recirculation and homing, hematopoiesis, and tumor metastasis. Transcripts for this gene undergo complex alternative splicing that results in many functionally distinct isoforms, however, the full length nature of some of these variants has not been determined. Alternative splicing is the basis for the structural and functional diversity of this protein, and may be related to tumor metastasis.

The protein CD80 (Cluster of Differentiation 80) is a molecule found on activated B cells and monocytes which provides a costimulatory signal necessary for T cell activation and survival. It is also known as B7.1. Its principal mode of action is by binding to CD28. Along with CD86, these molecules provide the necessary stimuli to prime T cells against antigens presented by antigen-presenting cells. CD80 and CD86 also bind to CTLA-4, a cell surface molecule expressed on activated T cells. Interactions between CD80 or CD86 with CTLA-4 decrease the response of T cells. Mouse research by scientists at Emory University showed that estrogen-related bone loss is linked to recently discovered pathways involving various proteins, such as CD80 and other functions. In a nutshell, reactive oxygen stimulates dendritic cells, which activate other immune cells to up-regulate production of CD80, the molecule co-responsible for T cell activation. “When this pathway is activated, it leads to increased T cell TNF production and ultimately to bone loss.” In turn, T cells produce a protein, Tumor Necrosis Factor, which increases the formation of osteoclasts in rodents and humans. Osteoclasts cause minerals to be released from the bone, so that calcium is taken into the bloodstream to be used for other functions of the body. Osteoclast differentiation is inhibited by osteoprotegerin; Estrogen stimulates osteoprotegerin production.

This gene encodes a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Tetraspanins are cell surface glycoproteins with four transmembrane domains that form multimeric complexes with other cell surface proteins. The encoded protein functions in many cellular processes including differentiation, adhesion, and signal transduction, and expression of this gene plays a critical role in the suppression of cancer cell motility and metastasis.

The cell division control protein cdc2, also known as cyclin-dependent kinase 1 (Cdk1) or p34/cdk1, plays a key role in the control of the eukaryotic cell cycle, where it is required for entry into S-phase and mitosis. Cdc2 exists as a complex with both cyclin A and cyclin B. The best characterized of these associations is the Cdc2 p34 cyclin B complex, which is required for the G2 to M phase transition. Activation of Cdc2 is controlled at several steps including cyclin binding and phosphorylation of threonine 161. However, the critical regulatory step in activating cdc2 during progression into mitosis appears to be dephosphorylation of Tyr15 and Tyr14. Phosphorylation at Tyr15 and inhibition of Cdc2 is carried out by WEE1 and MIK protein kinases while Tyr15 dephosphorylation and activation of Cdc2 is carried out by the cdc25 phosphatase. The isoform CDC2deltaT is found in breast cancer tissues. Furthermore, cdc2/Cdk1 is a key mediator of neuronal cell death in brain development and degeneration.

The cell division control protein cdc2, also known as cyclin-dependent kinase 1 (Cdk1) or p34/cdk1, plays a key role in the control of the eukaryotic cell cycle, where it is required for entry into S-phase and mitosis. Cdc2 exists as a complex with both cyclin A and cyclin B. The best characterized of these associations is the Cdc2 p34 cyclin B complex, which is required for the G2 to M phase transition. Activation of Cdc2 is controlled at several steps including cyclin binding and phosphorylation of threonine 161. However, the critical regulatory step in activating cdc2 during progression into mitosis appears to be dephosphorylation of Tyr15 and Tyr14. Phosphorylation at Tyr15 and inhibition of Cdc2 is carried out by WEE1 and MIK protein kinases while Tyr15 dephosphorylation and activation of Cdc2 is carried out by the cdc25 phosphatase. The isoform CDC2deltaT is found in breast cancer tissues. Furthermore, cdc2/Cdk1 is a key mediator of neuronal cell death in brain development and degeneration.

E-Cadherin is a 120 kDa transmembrane glycoprotein that is localized in the adherens junctions of epithelial cells. There, it interacts with the cytoskeleton through the associated cytoplasmic catenin proteins. In addition to being a calcium-dependent adhesion molecule, E-Cadherin is also a critical regulator of epithelial junction formation. Its association with catenins is necessary for cell-cell adhesion. These E-cadherin/catenin complexes associate with corical actin bundles at both the zonula adherens and the lateral adhesion plaques. Tyrosine phosphorylation can disrupt these complexes, leading to changes in cell adhesion properties. E-Cadherin expression is often down-regulated in highly invasive, poorly differentiated carcinomas. Increased expression of E-Cadherin in these cells reduces invasiveness. Thus, loss of expression or function of E-Cadherin appears to be an important step in tumorigenic progression.Tissue specificity: Non-neural epithelial tissues.

E-Cadherin is a 120 kDa transmembrane glycoprotein that is localized in the adherens junctions of epithelial cells. There, it interacts with the cytoskeleton through the associated cytoplasmic catenin proteins. In addition to being a calcium-dependent adhesion molecule, E-Cadherin is also a critical regulator of epithelial junction formation. Its association with catenins is necessary for cell-cell adhesion. These E-cadherin/catenin complexes associate with corical actin bundles at both the zonula adherens and the lateral adhesion plaques. Tyrosine phosphorylation can disrupt these complexes, leading to changes in cell adhesion properties. E-Cadherin expression is often down-regulated in highly invasive, poorly differentiated carcinomas. Increased expression of E-Cadherin in these cells reduces invasiveness. Thus, loss of expression or function of E-Cadherin appears to be an important step in tumorigenic progression.Tissue specificity: Non-neural epithelial tissues.

p27 KIP 1 is a cell cycle regulatory mitotic inhibitor of cdk activity. p27 KIP 1 is a candidate tumor suppressor gene, and has been proposed to function as a possible mediator of TGF beta induced G1 arrest. p27 KIP 1 is up regulated in response to antimitogenic stimuli. The increased protein expression of p27 results in cellular arrest by binding to cyclin/Cdk complexes such as cyclin D1/Cdk4. Decreased levels of p27Kip1, mainly due to proteosomal degradation, are found in various epithelial tumors originating from lung, breast, colon, ovary, esophagus, thyroid and prostate.Tissue specificity: Expressed in all tissues tested. Highest levels in skeletal muscle, lowest in liver and kidney.

The protein encoded by this gene is a tight-binding, strong inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations in this gene are implicated in sporadic cancers and Beckwith-Wiedemann syndorome, suggesting that this gene is a tumor suppressor candidate. Three transcript variants encoding two different isoforms have been found for this gene.Tissue specificity: Expressed in the heart, brain, lung, skeletal muscle, kidney, pancreas and testis. High levels are seen in the placenta while low levels are seen in the liver.

This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, MDM1, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene.

Carcino Embryonic Antigen (CEA) is synthesised during development in the fetal gut, and is re-expressed in increased amounts in intestinal carcinomas and several other tumors. Antibodies to CEA are useful in identifying the origin of various metastatic adenocarcinomas and in distinguishing pulmonary adenocarcinomas (60 to 70% are CEA+) from pleural mesotheliomas (rarely or weakly CEA+).The carcinoembryonic antigen (CEA) is a member of a large family of glycoproteins and a useful tumor marker for adenocarcinoma.Tissue specificity: Found in adenocarcinomas of endodermally derived digestive system epithelium and fetal colon.

Carcino Embryonic Antigen (CEA) is synthesised during development in the fetal gut, and is re-expressed in increased amounts in intestinal carcinomas and several other tumors. Antibodies to CEA are useful in identifying the origin of various metastatic adenocarcinomas and in distinguishing pulmonary adenocarcinomas (60 to 70% are CEA+) from pleural mesotheliomas (rarely or weakly CEA+). The carcinoembryonic antigen (CEA) is a member of a large family of glycoproteins and a useful tumor marker for adenocarcinoma. Tissue specificity: Found in adenocarcinomas of endodermally derived digestive system epithelium and fetal colon.

CHK2: CHK2 checkpoint homolog (S. pombe). In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Three transcript variants encoding different isoforms have been found for this gene.

MECT1 (also known as MucoEpidermoid Carcinoma Translocated 1) functions as a transcriptional coactivator for CREB1, which activates transcription through both consensus and variant cAMP response element (CRE) sites. MECT1 does not appear to modulate CREB1 DNA-binding activity but enhances the interaction of CREB1 with TAF4/TAFII-130. MECT1 translocates with MAML2 (MasterMind-Like Protein 2) to yield a fusion oncogene: t(11;19) (q21;p13). This translocation occurs in mucoepidermoid carcinomas, benign Warthin tumors and clear cell hidradenomas. The novel fusion product that results disrupts the Notch signaling pathway. The fusion protein consists of the N-terminus of MECT1 joined to the C-terminus of MAML2. The reciprocal fusion protein consisting of the N-terminus of MAML2 joined to the C-terminus of MECT1 has been detected in a small number of mucoepidermoid carcinomas. Multiple isoforms have been reported for the MECT1 protein. Tissue specificity: Highly expressed in adult and fetal brain. Located to specific regions such as the prefrontal cortex and cerebellum. Very low expression in other tissues such as heart, spleen, lung, skeletal muscle, salivary gland, ovary and kidney.

Casein kinase II (CK2) is a constitutively active, ubiquitously expressed serine/threonine protein kinasethat is thought to have a regulatory function in cell proliferation, cell differentiation and apoptosis. CK2functions as a tetrameric complex consisting of two regulatory beta-subunits and two catalytic units (alphaand alpha’) in a homomeric or heteromeric conformation. Whilst the alpha- and alpha’-subunits arecatalytically identical, proteins that regulate CK2, such as cdc2 and Hsp90, preferentially bind to thealpha and not the alpha’-subunit. CK2 can phosphorylate a number of key intracellular signaling proteinsimplicated in tumor suppression (p53 and PTEN) and tumorigenesis (myc, jun, NF-kappaB). CK2 is also thoughtto influence Wnt signaling via beta-catenin phosphorylation and the PI 3-K signaling pathway via thephosphorylation of Akt.

This gene is a member of the BORIS + CTCF gene family and encodes a transcriptional regulator protein with 11 highly conserved zinc finger (ZF) domains. This nuclear protein is able to use different combinations of the ZF domains to bind different DNA target sequences and proteins. Depending upon the context of the site, the protein can bind a histone acetyltransferase (HAT)-containing complex and function as a transcriptional activator or bind a histone deacetylase (HDAC)-containing complex and function as a transcriptional repressor. If the protein is bound to a transcriptional insulator element, it can block communication between enhancers and upstream promoters, thereby regulating imprinted expression. Mutations in this gene have been associated with invasive breast cancers, prostate cancers, and Wilms’ tumors.Tissue specificity: Ubiquitous. Absent in primary spermatocytes.

This gene is overexpressed in breast cancer and squamous cell carcinomas of the head and neck. The encoded protein is localized in the cytoplasm and in areas of the cell-substratum contacts. This gene has two roles: (1) regulating the interactions between components of adherens-type junctions and (2) organizing the cytoskeleton and cell adhesion structures of epithelia and carcinoma cells. During apoptosis, the encoded protein is degraded in a caspase-dependent manner. The aberrant regulation of this gene contributes to tumor cell invasion and metastasis. Three splice variants that encode different isoforms have been identified for this gene. (provided by RefSeq)

This gene, CYP1A1, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. The enzyme’s endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. The gene has been associated with lung cancer risk. A related family member, CYP1A2, is located approximately 25 kb away from CYP1A1 on chromosome 15.

Biochemically, most members of the CK family fall into one of two classes, type I (acidic polypeptides) and type II (basic polypeptides). The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. Cytokeratins comprise a diverse group of intermediate filament proteins (IFPs) that are expressed as pairs in both keratinized and non-keratinized epithelial tissue. Cytokeratins play a critical role in differentiation and tissue specialization and function to maintain the overall structural integrity of epithelial cells. Cytokeratins have been found to be useful markers of tissue differentiation which is directly applicable to the characterization of malignant tumors.

Biochemically, most members of the CK family fall into one of two classes, type I (acidic polypeptides) and type II (basic polypeptides). The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. Cytokeratins comprise a diverse group of intermediate filament proteins (IFPs) that are expressed as pairs in both keratinized and non-keratinized epithelial tissue. Cytokeratins play a critical role in differentiation and tissue specialization and function to maintain the overall structural integrity of epithelial cells. Cytokeratins have been found to be useful markers of tissue differentiation which is directly applicable to the characterization of malignant tumors.

DDR1: discoidin domain receptor tyrosine kinase 1. Receptor tyrosine kinases (RTKs) play a key role in the communication of cells with their microenvironment. These molecules are involved in the regulation of cell growth, differentiation and metabolism. The protein encoded by this gene is a RTK that is widely expressed in normal and transformed epithelial cells and is activated by various types of collagen. This protein belongs to a subfamily of tyrosine kinase receptors with a homology region to the Dictyostelium discoideum protein discoidin I in their extracellular domain. Its autophosphorylation is achieved by all collagens so far tested (type I to type VI). In situ studies and Northern-blot analysis showed that expression of this encoded protein is restricted to epithelial cells, particularly in the kidney, lung, gastrointestinal tract, and brain. In addition, this protein is significantly over-expressed in several human tumors from breast, ovarian, esophageal, and pediatric brain. This gene is located on chromosome 6p21.3 in proximity to several HLA class I genes. Alternative splicing of this gene results in multiple transcript variants.

Dkk-3 (Dickkopf-3) is a member of the dickkopf family. It is a 350 amino acid secreted glycoprotein that is composed of an N-terminal signal peptide and two conserved cysteine-rich domains, which are separated by a 12 amino acid linker region. This secreted protein is involved in embryonic development through its interactions with the Wnt signaling pathway. The expression of this gene is decreased in a variety of cancer cell lines and it may function as a tumor suppressor gene.

This gene encodes a protein that is a member of the dickkopf family. The secreted protein contains two cysteine rich regions and is involved in embryonic development through its interactions with the Wnt signaling pathway. The expression of this gene is decreased in a variety of cancer cell lines and it may function as a tumor suppressor gene. Alternative splicing results in multiple transcript variants encoding the same protein.

This gene encodes a transmembrane protein containing six epidermal growth factor repeats. The protein is involved in the differentiation of several cell types, including adipocytes; it is also thought to be a tumor suppressor. It is one of several imprinted genes located in a region of on chr 14q32. Certain mutations in this imprinted region can cause phenotypes similar to maternal and paternal uniparental disomy of chromosome 14 (UPD14). This gene is expressed from the paternal allele. A polymorphism within this gene has been associated with child and adolescent obesity. The mode of inheritance for this polymorphism is polar overdominance; this non-Mendelian inheritance pattern was first described in sheep with the callipyge phenotype, which is characterized by muscle hypertrophy and decreased fat mass.

The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein and another 2 members, E2F2 and E2F3, have an additional cyclin binding domain. This protein binds preferentially to retinoblastoma protein pRB in a cell-cycle dependent manner. It can mediate both cell proliferation and p53-dependent/independent apoptosis.

The protein encoded by this gene belongs to the EGR family of C2H2-type zinc-finger proteins. It is a nuclear protein and functions as a transcriptional regulator. The products of target genes it activates are required for differentitation and mitogenesis. Studies suggest this is a cancer suppresor gene.

Endothelial nitric-oxide synthase (eNOS), also known as NOS3, it is an important enzyme in the cardiovascular system. It is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. Nitric oxide is synthesized from L-arginine by nitric oxide synthases. Variations in this gene are associated with susceptibility to coronary spasm.

EP300: E1A binding protein p300. This gene encodes the adenovirus E1A-associated cellular p300 transcriptional co-activator protein. It functions as histone acetyltransferase that regulates transcription via chromatin remodeling and is important in the processes of cell proliferation and differentiation. It mediates cAMP-gene regulation by binding specifically to phosphorylated CREB protein. This gene has also been identified as a co-activator of HIF1A (hypoxia-inducible factor 1 alpha), and thus plays a role in the stimulation of hypoxia-induced genes such as VEGF. Defects in this gene are a cause of Rubinstein-Taybi syndrome and may also play a role in epithelial cancer.

EPH receptor A2 (EphA2), with 976-amino acid protein (about 107 kDa), belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EphA1, EphA2, EphA3, EphA4, EphA5, EphA6, EphA7, EphA8, EphA10, EphB1, EphB2, EphB3, EphB4 and EphB6 are Eph family receptors for Ephrin family ligands. In normal cells, EphA2 negatively regulates cell growth and invasiveness. EphA2 is overexpressed by many human cancers, and is often associated with poor prognostic features. The clinical significance of the expression of EphA2 was observed in breast, prostate, colon, skin, cervical, ovarian, and lung cancers.EphA2 may serve as a novel target for bladder cancer, colonic adenocarcinoma and ovarian cancer therapy.

EPH receptor B4 (EphB4), with 987-amino acid protein (about 108kDa), belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. The Eph receptor tyrosine kinases and their ligands, the ephrins, regulate numerous biological processes in developing and adult tissues and have been implicated in cancer progression and in pathological forms of angiogenesis. EphB4 acts as a negative regulator of blood vessel branching and vascular network formation, switching the vascularization program from sprouting angiogenesis to circumferential vessel growth. EphB4 and its ligand ephrinB2 express in several kinds of tumor cells and correlate with tumorigenesis. EphB4 is thus a potential candidate as a predictor of disease outcome in several kinds of tumor and as target for novel therapy.

ERBB2: v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian). This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized.

ERBB2: v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian). This gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. This protein has no ligand binding domain of its own and therefore cannot bind growth factors. However, it does bind tightly to other ligand-bound EGF receptor family members to form a heterodimer, stabilizing ligand binding and enhancing kinase-mediated activation of downstream signalling pathways, such as those involving mitogen-activated protein kinase and phosphatidylinositol-3 kinase. Allelic variations at amino acid positions 654 and 655 of isoform a (positions 624 and 625 of isoform b) have been reported, with the most common allele, Ile654/Ile655, shown here. Amplification and/or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. Alternative splicing results in several additional transcript variants, some encoding different isoforms and others that have not been fully characterized

ERBB3: v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian). This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized.

ERBB3, v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian). It is a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized.

ERBB3: v-erb-b2 erythroblastic leukemia viral oncogene homolog 3 (avian). This gene encodes a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. This membrane-bound protein has a neuregulin binding domain but not an active kinase domain. It therefore can bind this ligand but not convey the signal into the cell through protein phosphorylation. However, it does form heterodimers with other EGF receptor family members which do have kinase activity. Heterodimerization leads to the activation of pathways which lead to cell proliferation or differentiation. Amplification of this gene and/or overexpression of its protein have been reported in numerous cancers, including prostate, bladder, and breast tumors. Alternate transcriptional splice variants encoding different isoforms have been characterized. One isoform lacks the intermembrane region and is secreted outside the cell. This form acts to modulate the activity of the membrane-bound form. Additional splice variants have also been reported, but they have not been thoroughly characterized.

ER (estrogen receptor 1) a member of the steroid receptor superfamily, contains highly conserved DNA binding (DBD) and ligand binding domains (LBD). Through its estrogen-independent and estrogen-dependent activation domains (AF-1 and AF-2, respectively), ER regulates transcription by recruiting coactivator proteins and interacting with general transcriptional machinery. Phosphorylation provides an important mechanism to regulate ER activity. ER is phosphorylated on multiple sites. Serines 104, 106, 118 and 167 are located in the amino-terminal transcription activation function domain AF-1, and phosphorylation of these serines plays an important role in regulating ER activity. Ser118 may be the substrate of the transcription regulatory kinase cdK7. Ser167 may be phosphorylated by p90RSK and Akt. Phosphorylation of Ser167 may confer tamoxifen resistance in breast cancer patients.

ESR1: estrogen receptor 1. This gene encodes an estrogen receptor, a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. The protein localizes to the nucleus where it may form a homodimer or a heterodimer with estrogen receptor 2. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone. Estrogen receptors are also involved in pathological processes including breast cancer, endometrial cancer, and osteoporosis. Alternative splicing results in several transcript variants, which differ in their 5′ UTRs and use different promoters.

ESR1: estrogen receptor 1. This gene encodes an estrogen receptor, a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. The protein localizes to the nucleus where it may form a homodimer or a heterodimer with estrogen receptor 2. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone. Estrogen receptors are also involved in pathological processes including breast cancer, endometrial cancer, and osteoporosis. Alternative splicing results in several transcript variants, which differ in their 5′ UTRs and use different promoters.

This gene encodes an estrogen receptor, a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. The protein localizes to the nucleus where it may form a homodimer or a heterodimer with estrogen receptor 2. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone. Estrogen receptors are also involved in pathological processes including breast cancer, endometrial cancer, and osteoporosis.

ESR1: estrogen receptor 1. This gene encodes an estrogen receptor, a ligand-activated transcription factor composed of several domains important for hormone binding, DNA binding, and activation of transcription. The protein localizes to the nucleus where it may form a homodimer or a heterodimer with estrogen receptor 2. Estrogen and its receptors are essential for sexual development and reproductive function, but also play a role in other tissues such as bone. Estrogen receptors are also involved in pathological processes including breast cancer, endometrial cancer, and osteoporosis. Alternative splicing results in several transcript variants, which differ in their 5′ UTRs and use different promoters.

The ETS1 is a transcription factor known to regulate expression of a number of genes involved in extracellular matrix remodeling. ETS1 is absent from normal gastric epithelium but is expressed in approximately 60% of gastric carcinomas and oral squamous cell carcinomas with a significant correlation to the tumor stage.

The ETS1 is a transcription factor known to regulate expression of a number of genes involved in extracellular matrix remodeling. ETS1 is absent from normal gastric epithelium but is expressed in approximately 60% of gastric carcinomas and oral squamous cell carcinomas with a significant correlation to the tumor stage.

This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Activation of this gene may be an important early step in cell growth and intracellular signal transduction pathways triggered in response to certain neural peptides or to cell interactions with the extracellular matrix. At least four transcript variants encoding four different isoforms have been found for this gene, but the full-length natures of only two of them have been determined. Tissue specificity: Expressed in all organs tested, in lymphoid cell lines, but most abundantly in brain.RD: Focal adhesion kinase 1 (FAK) is a ubiquitously expressed non-receptor protein tyrosine kinase that is concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. This cellular localization is directed by a “Focal Adhesion Targeting” (FAT) sequence, a 125 amino acid sequence at the C-terminus. FAK plays an important role in migration, cell spreading, differentiation, cytoskeleton protein phosphorylation, apoptosis and acceleration of the G1 to S phase transition of the cell cycle. It associates with several different signaling proteins such as Src-family PTKs, p130Cas, Shc, Grb2, PI 3-kinase, and paxillin. This enables FAK to function within a network of integrin-stimulated signaling pathways leading to the activation of targets such as the ERK and JNK/mitogen-activated protein kinase pathways. FAK is also linked to oncogenes at biochemical and functional levels. Increased expression and/or activity of FAK in various tumors has been correlated with enhanced migration and invasiveness of human tumor cells in addition to promoting increased cell proliferation.

This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Activation of this gene may be an important early step in cell growth and intracellular signal transduction pathways triggered in response to certain neural peptides or to cell interactions with the extracellular matrix. At least four transcript variants encoding four different isoforms have been found for this gene, but the full-length natures of only two of them have been determined. Tissue specificity: Expressed in all organs tested, in lymphoid cell lines, but most abundantly in brain.RD: Focal adhesion kinase 1 (FAK) is a ubiquitously expressed non-receptor protein tyrosine kinase that is concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. This cellular localization is directed by a “Focal Adhesion Targeting” (FAT) sequence, a 125 amino acid sequence at the C-terminus. FAK plays an important role in migration, cell spreading, differentiation, cytoskeleton protein phosphorylation, apoptosis and acceleration of the G1 to S phase transition of the cell cycle. It associates with several different signaling proteins such as Src-family PTKs, p130Cas, Shc, Grb2, PI 3-kinase, and paxillin. This enables FAK to function within a network of integrin-stimulated signaling pathways leading to the activation of targets such as the ERK and JNK/mitogen-activated protein kinase pathways. FAK is also linked to oncogenes at biochemical and functional levels. Increased expression and/or activity of FAK in various tumors has been correlated with enhanced migration and invasiveness of human tumor cells in addition to promoting increased cell proliferation.

This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Activation of this gene may be an important early step in cell growth and intracellular signal transduction pathways triggered in response to certain neural peptides or to cell interactions with the extracellular matrix. At least four transcript variants encoding four different isoforms have been found for this gene, but the full-length natures of only two of them have been determined. Tissue specificity: Expressed in all organs tested, in lymphoid cell lines, but most abundantly in brain.RD: Focal adhesion kinase 1 (FAK) is a ubiquitously expressed non-receptor protein tyrosine kinase that is concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. This cellular localization is directed by a “Focal Adhesion Targeting” (FAT) sequence, a 125 amino acid sequence at the C-terminus. FAK plays an important role in migration, cell spreading, differentiation, cytoskeleton protein phosphorylation, apoptosis and acceleration of the G1 to S phase transition of the cell cycle. It associates with several different signaling proteins such as Src-family PTKs, p130Cas, Shc, Grb2, PI 3-kinase, and paxillin. This enables FAK to function within a network of integrin-stimulated signaling pathways leading to the activation of targets such as the ERK and JNK/mitogen-activated protein kinase pathways. FAK is also linked to oncogenes at biochemical and functional levels. Increased expression and/or activity of FAK in various tumors has been correlated with enhanced migration and invasiveness of human tumor cells in addition to promoting increased cell proliferation.

FES (feline sarcoma oncogene) and Fer are the only two members of a unique family of cytoplasmic protein tyrosine kinases. FES and Fer contain a central Src homology-2 (SH2) domain and a carboxy-terminal tyrosine kinase catalytic domain. They are structurally distinguished from other members of cytoplasmic protein tyrosine kinase subfamilies by the presence of amino-terminal Fer/CIP4 homology and coiled-coil domains. FES was originally identified as an oncogene from avian and feline retroviruses. Human c-Fes has been implicated in myeloid, vascular endothelial and neuronal cell differentiation. FES has tyrosine-specific protein kinase activity and that activity is required for maintenance of cellular transformation. Mutations may activate the FES kinase and thereby contribute to cancer. However, recent data strongly suggests that the c-FES protein-tyrosine kinase is a tumor suppressor rather than a dominant oncogene in colorectal cancer.

FES (feline sarcoma oncogene) and Fer are the only two members of a unique family of cytoplasmic protein tyrosine kinases. FES and Fer contain a central Src homology-2 (SH2) domain and a carboxy-terminal tyrosine kinase catalytic domain. They are structurally distinguished from other members of cytoplasmic protein tyrosine kinase subfamilies by the presence of amino-terminal Fer/CIP4 homology and coiled-coil domains. FES was originally identified as an oncogene from avian and feline retroviruses. Human c-Fes has been implicated in myeloid, vascular endothelial and neuronal cell differentiation. FES has tyrosine-specific protein kinase activity and that activity is required for maintenance of cellular transformation. Mutations may activate the FES kinase and thereby contribute to cancer. However, recent data strongly suggests that the c-FES protein-tyrosine kinase is a tumor suppressor rather than a dominant oncogene in colorectal cancer.

FGFR4: fibroblast growth factor receptor 4. Entrez Protein NP_002002. It is a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. The genomic organization of this gene, compared to members 1-3, encompasses 18 exons rather than 19 or 20. Although alternative splicing has been observed, there is no evidence that the C-terminal half of the IgIII domain of this protein varies between three alternate forms, as indicated for members 1-3. This particular family member preferentially binds acidic fibroblast growth factor and, although its specific function is unknown, it is overexpressed in gynecological tumor samples, suggesting a role in breast and ovarian tumorigenesis.

This gene encodes a tyrosine kinase receptor for vascular endothelial growth factors C and D. The protein is thought to be involved in lymphangiogenesis and maintenance of the lymphatic endothelium. Mutations in this gene cause hereditary lymphedema type IA. Tissue specificity: Placenta, lung, heart, and kidney, does not seem to be expressed in pancreas and brain. VEGFR-3 is induced in all endothelial cells (EC’s) during early embryogenesis, and its expression eventually disappears from the vascular endothelial cells of adult tissues. VEGFR-3 is constitutively expressed in the adult lymphatic endothelium. Although VEGFR-3 is not expressed in adult blood vessels, it is induced in vascular endothelial cells of tumor-bearing tissues.VEGFR-3 expression in adults is largely restricted to the endothelial cells of the lymphatic system, and high endothelial venules (HEV).

This gene belongs to subfamily P of the forkhead box (FOX) transcription factor family. Forkhead box transcription factors play important roles in the regulation of tissue- and cell type-specific gene transcription during both development and adulthood. Forkhead box P1 protein contains both DNA-binding- and protein-protein binding-domains. This gene may act as a tumor suppressor as it is lost in several tumor types and maps to a chromosomal region (3p14.1) reported to contain a tumor suppressor gene(s). Alternative splicing results in multiple transcript variants encoding different isoforms.

GFAP, a class-III intermediate filament, is a cell-specific marker that, during the development of the central nervous system, distinguishes astrocytes from other glial cells.Tissue specificity: Expressed in cells lacking fibronectin.ABCAM:It is heavily, and specifically, expressed in astrocytes and certain other astroglia in the central nervous system, in satellite cells in peripheral ganglia, and in non myelinating Schwann cells in peripheral nerves.In addition many types of brain tumor, presumably derived from astrocytic cells, heavily express GFAP. GFAP is also found in the lens epithelium, Kupffer cells of the liver, in some cells in salivary tumors and has been reported in erythrocytes.

Glycogen synthase kinase 3 (GSK-3), a serine-threonine kinase with two isoforms (alpha and beta), was originally discovered as a key enzyme in glycogen metabolism. GSK-3 was subsequently shown to function in cell division, proliferation, motility and survival. GSK-3 plays a role in a number of pathological conditions including cancer and diabetes and is increasingly seen as an important component of neurological diseases. GSK-3 phosphorylates tau and presenilin-1, which are involved in the development of Alzheimer’s disease. Both isoforms of GSK-3 are ubiquitously expressed, although particularly high levels of GSK-3beta are found in the brain where it is involved in synaptic plasticity, possibly via regulation of NMDA receptor trafficking. GSK-3 phosphorylates over 40 different substrates including signaling proteins, transcription factors and structural proteins, and is part of the signal transduction cascade of a large number of growth factors and cytokines. The activity of GSK is regulated by phosphorylation (Akt: Akt-mediated phosphorylation at Ser21 of GSK-3α and Ser9 of GSK-3β, S6K, RSK, PKA and PKC), dephosphorylation (PP1 and PP2A), and by binding to protein complexes (with beta-catenin, axin, CK1 and the APC complex).

Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual’s susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene.

Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and are known to be highly polymorphic. These genetic variations can change an individual’s susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of certain drugs. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene.

GSTP1 (glutathione-S-transferase, pi 1), also called GST3/DFN7, is a family of enzymes that play an important role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. GSTP1 act like a tumor suppressor gene, which when inactivated leads to tumor growth, and the -class glutathione S-transferase is commonly inactivated by somatic CpGisland hypermethylation in cancers of the prostate, liver, and breast. Methylation of regulatory sequences at the GSTP1 gene locus is found in the vast majority (>90%) of prostate carcinomas and is associated with transcriptional down-regulation.

Hyaluronan or hyaluronic acid (HA) is a high molecular weight unbranched polysaccharide synthesized by a wide variety of organisms from bacteria to mammals, and is a constituent of the extracellular matrix. It consists of alternating glucuronic acid and N-acetylglucosamine residues that are linked by beta-1-3 and beta-1-4 glycosidic bonds. HA is synthesized by membrane-bound synthase at the inner surface of the plasma membrane, and the chains are extruded through pore-like structures into the extracellular space. It serves a variety of functions, including space filling, lubrication of joints, and provision of a matrix through which cells can migrate. HA is actively produced during wound healing and tissue repair to provide a framework for ingrowth of blood vessels and fibroblasts. Changes in the serum concentration of HA are associated with inflammatory and degenerative arthropathies such as rheumatoid arthritis. In addition, the interaction of HA with the leukocyte receptor CD44 is important in tissue-specific homing by leukocytes, and overexpression of HA receptors has been correlated with tumor metastasis. HAS1 is a member of the newly identified vertebrate gene family encoding putative hyaluronan synthases, and its amino acid sequence shows significant homology to the hasA gene product of Streptococcus pyogenes, a glycosaminoglycan synthetase (DG42) from Xenopus laevis, and a recently described murine hyaluronan synthase.

Hyaluronan or hyaluronic acid (HA) is a high molecular weight unbranched polysaccharide synthesized by a wide variety of organisms from bacteria to mammals, and is a constituent of the extracellular matrix. It consists of alternating glucuronic acid and N-acetylglucosamine residues that are linked by beta-1-3 and beta-1-4 glycosidic bonds. HA is synthesized by membrane-bound synthase at the inner surface of the plasma membrane, and the chains are extruded through pore-like structures into the extracellular space. It serves a variety of functions, including space filling, lubrication of joints, and provision of a matrix through which cells can migrate. HA is actively produced during wound healing and tissue repair to provide a framework for ingrowth of blood vessels and fibroblasts. Changes in the serum concentration of HA are associated with inflammatory and degenerative arthropathies such as rheumatoid arthritis. In addition, the interaction of HA with the leukocyte receptor CD44 is important in tissue-specific homing by leukocytes, and overexpression of HA receptors has been correlated with tumor metastasis. HAS2 is a member of the newly identified vertebrate gene family encoding putative hyaluronan synthases, and its amino acid sequence shows significant homology to glycosaminoglycan synthetase (DG42) from Xenopus laevis, and human and murine hyaluronan synthase 1.

USP7 or HAUSP is a ubiquitin specific protease or a deubiquitylating enzyme that cleaves ubiquitin from its substrates. Since ubiquitylation (polyubiquitination) is most commonly associated with the stability and degradation of cellular proteins, HAUSP acitivity generally stabilizes its substrate proteins. HAUSP is most popularly known as a direct antagonist of Mdm2, the E3 ubiquitin ligase for the tumor suppressor protein, p53.Normally, p53 levels are kept low in part due to Mdm2-mediated ubiquitylation and degradation of p53. Interestingly, in response to oncogenic insults, HAUSP can deubiquitinate p53 and protect p53 from Mdm2-mediated degradation, indicating that it may possess a tumor suppressor function for the immediate stabilization of p53 in response to stress. Another important role of HAUSP function involves the oncogenic stabilization of p53. Oncogenes such as Myc and E1A are thought to activate p53 through a p19 alternative reading frame (p19ARF, also called ARF)-dependent pathway, although some evidence suggests ARF is not essential in this process. An intriguing possibility is that HAUSP provides an alternative pathway for safeguarding the cell against oncogenic insults.

HDAC3: histone deacetylase 3, also known as HD3, RPD3, RPD3-2. Entrez Protein NC_000005. Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter. It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumor suppressor gene.

HDAC3: histone deacetylase 3, also known as HD3, RPD3, RPD3-2. Entrez Protein NC_000005. Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter. It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumor suppressor gene.

The C-erbB-2 (HER-2/neu) gene encodes a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. Amplification or overexpression of this gene has been reported in numerous cancers, including breast and ovarian tumors. High levels of c-erbB-2 were associated with estrogen receptor (ER) and progesterone receptor negativity.     Overexpression of the c-erbB-2 oncogene has been shown to be associated with poor prognosis in ovarian and breast cance, The level of increased Neu expression can be a predictor of disease prognosis

Hypoxia-inducible factor-1 (HIF1) is a transcription factor found in mammalian cells cultured under reduced oxygen tension that plays an essential role in cellular and systemic homeostatic responses to hypoxia. HIF1 is a heterodimer composed of an alpha subunit and a beta subunit. The beta subunit has been identified as the aryl hydrocarbon receptor nuclear translocator (ARNT). This gene encodes the alpha subunit of HIF-1. Overexpression of a natural antisense transcript (aHIF) of this gene has been shown to be associated with nonpapillary renal carcinomas. Two alternative transcripts encoding different isoforms have been identified. (provided by RefSeq) Tissue specificity: Expressed in most tissues with highest levels in kidney and heart. Overexpressed in the majority of common human cancers and their metastases, due to the presence of intratumoral hypoxia and as a result of mutations in genes encoding oncoproteins and tumor suppressors.

The hexokinases utilize Mg-ATP as a phosphoryl donor to catalyze the first step of intracellular glucose metabolism, the conversion of glucose to glucose- 6-phosphate. Four hexokinase isoenzymes have been identified, including hexokinase I (HXK I), hexokinase II (HXK II), hexokinase III (HXK III) and hexokinase IV (HXK IV, also designated glucokinase or GCK). Hexokinases I-III each contain an N-terminal cluster of hydrophobic amino acids. Glucokinase lacks the N-terminal hydrophobic cluster. The hydrophobic cluster is thought to be necessary for membrane binding. This is substantiated by the finding that glucokinase has lower affinity for glucose than do the other hexokinases .Hexokinase 2 is the predominant hexokinase isozyme expressed in insulin-responsive tissues such as skeletal muscle. Expression of this gene is insulin-responsive, and studies in rat suggest that it is involved in the increased rate of glycolysis seen in rapidly growing cancer cells.

The protein encoded by this gene is primarily found in the nucleolus, where it can bind to the 5′ UTR of the insulin-like growth factor II leader 3 mRNA and may repress translation of insulin-like growth factor II during late development. The encoded protein contains several KH domains, which are important in RNA binding and are known to be involved in RNA synthesis and metabolism.Tissue specificity: Expressed in fetal liver, fetal lung, fetal kidney, fetal thymus, fetal placenta, fetal follicles of ovary and gonocytes of testis, growing oocytes, spermatogonia and semen (at protein level). Expressed in cervix adenocarcinoma, in testicular, pancreatic and renal-cell carcinomas (at protein level). Expressed ubiquitously during fetal development at 8 and 14 weeks of gestation. Expressed in ovary, testis, brain, placenta, pancreatic cancer tissues and pancreatic cancer cell lines .IMP-3 is a marker for carcinomas and high-grade dysplastic lesions of pancreatic ductal epithelium.

IGFBP2: insulin-like growth factor binding protein 2. IGFBP2 is a member of the ISGBP family which bind various IGFs. IGFBP2 is overexpressed in a wide spectrum of other cancers, including glioma, prostate cancer, synovial sarcoma, neuroblastoma, colon cancer, adrenocortical cancer, lung cancer, Wilms’ tumor, and hepatoblastoma. The overexpression of IGFBP2 also correlates with the aggressiveness of some tumors. IGFBP2 activates the expression of matrix metalloprotease 2, which contributes to cell invasiveness.

INHA (A-inhibin subunit precursor, inhibin alpha subunit ), also called inhibin (alpha) ,which is located on chromosome 2q33-q36. Inhibin is a gonadal protein that preferentially suppresses the secretion of pituitary follicle-stimulating hormone (FSH). Inhibin comprises of two subunits,Inhibin A and B. Inhibin has been shown to regulate gonadal stromal cell proliferation negatively and to have tumor suppressor activity. In addition, serum levels of inhibin have been shown to reflect the size of granulosa cell tumors and can therefore be used as a marker for primary as well as recurrent disease. In addition to their role in endocrine feedback in the reproductive sytem, inhibins subserve local regulatory roles in numerous extragonadal tissues, including brain, adrenal,bone marrow, placenta, and most notably anterior pituitary. Inhibin  alpha subunit gene expression is down regulated in human prostate cancer, suggesting a tumor suppressive role.

Integrins are heterodimeric proteins made up of alpha and beta subunits. At least 18 alpha and 8 beta subunits have been described in mammals. Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells. This gene encodes a beta subunit. Multiple alternatively spliced transcript variants which encode different protein isoforms have been found for this gene.

Integrins are heterodimeric proteins made up of alpha and beta subunits. At least 18 alpha and 8 beta subunits have been described in mammals. Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells. This gene encodes a beta subunit. Multiple alternatively spliced transcript variants which encode different protein isoforms have been found for this gene.

The c-Kit proto-oncogene is a member of the receptor tyrosine kinase family and, more specifically, is closely related to the platelet derived growth factor receptor (PDGFR). c-Kit, the normal cellular homolog of the HZ4-feline sarcoma virus transforming gene (v-Kit), encodes a transmembrane receptor. c-Kit regulates a variety of biological responses including chemotaxis, cell prolif- eration, apoptosis and adhesion. c-Kit is also identical with the product of the W locus in mice and, as such, is integral to the development of mast cells and hematopoiesis. The ligand for the c-Kit receptor (KL) has been identified and is encoded at the murine steel (SI) locus. Kit is the human homolog of the proto- oncogene c-Kit. Mutations in Kit are integral for tumor growth and progression in various cancers.

Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Its protein product is a protease present in seminal plasma. It is thought to function normally in the liquefaction of seminal coagulum, presumably by hydrolysis of the high molecular mass seminal vesicle protein. Serum level of this protein, called PSA in the clinical setting, is useful in the diagnosis and monitoring of prostatic carcinoma. Alternate splicing of this gene generates several transcript variants encoding different isoforms.

LAMB1: laminin, beta 1. Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the beta chain isoform laminin, beta 1. The beta 1 chain has 7 structurally distinct domains which it shares with other beta chain isomers. The C-terminal helical region containing domains I and II are separated by domain alpha, domains III and V contain several EGF-like repeats, and domains IV and VI have a globular conformation. Laminin, beta 1 is expressed in most tissues that produce basement membranes, and is one of the 3 chains constituting laminin 1, the first laminin isolated from Engelbreth-Holm-Swarm (EHS) tumor. A sequence in the beta 1 chain that is involved in cell attachment, chemotaxis, and binding to the laminin receptor was identified and shown to have the capacity to inhibit metastasis.

Lck (lymphocyte-specific protein tyrosine kinase), with 509-amino acid protein (about 56kDa), belongs to the Src non-receptor tyrosine kinases family. By virtue of common structural motifs, the Src family is composed of nine members in vertebrates, including Src, Yes, Fgr, Frk, Fyn, Lyn, Hck, Lck and Blk. Lck is expressed predominantly in T cells and is localized to the inner surface of the plasma membrane. Lck is activated after T cell stimulation and is required for T-cell proliferation and IL-2 production. Aberrant expression or activation of Lck kinase has been reported in both lymphoid and nonlymphoid malignancies. In addition, inhibition of Lck has been a target to prevent lymphocyte activation and acute rejection.

LIM domain containing preferred translocation partner in lipoma. The Zyxin family of proteins contains five members, Ajuba, LIMD1, LPP,TRIP6 and Zyxin. LPP (LIM-containing lipoma-preferred partner), a LIM domain-containing scaffolding protein contains three LIM domains at its carboxy
terminus, which are preceded by a proline-rich pre-LIM region containing a number of protein interaction domains. LPP, an 80 kDa protein, localizes to sites of cell adhesion, such as focal adhesions and cell-cell contacts,and shuttles to the nucleus where it has transcriptional activation capacity.The human LPP gene maps to chromosomal location 3q28, and preferentially
translocates to the HMGIC gene in a subclass of human benign mesenchymal tumors known as lipomas.

Mammaglobin is a gene that is expressed almost exclusively in the normal breast epithelium and human breast cancer. It is a member of the secretoglobin gene family and forms a heterodimer with lipophilin B. It has been suggested that mammaglobin may be a useful marker for breast cancer clinical research. Studies investigating the detection of mRNA by RT PCR from circulating carcinoma cells in the peripheral blood of breast cancer patients have shown that mammaglobin is a highly specific marker and correlates with several prognostic factors, such as lymph node involvement.

MAP2K4(mitogen-activated protein kinase kinase 4), which is located on chromosome 17p11.2, with 399-amino acid protein (about 45 kDa), belongs to the  family of protein kinases located upstream of the MAP kinases and responsible for their activation has been identified.  MEK-4 (also called MEK4/MKK4) activates both p38 and JNK MAP kinases.
MKK4 is a central mediator in the stress activated protein kinase signaling pathway that responds to a number of cellular and environmental stressors. By phosphorylating MAP kinases such as JNK,MKK4 can ultimately transmit stress signals to nuclear transcription factors that mediate various processes including proliferation, apoptosis, and differentiation. Its distinct biological functions have been identified for MKK4 including a role in development, hepatogenesis, and metastasis suppression.

The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various cell stimuli, and targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli. The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha induced apoptosis. This kinase is also involved in UV radiation induced apoptosis, which is thought to be related to cytochrom c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and differentiation. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.

MATK (megakaryocyte-associated tyrosine kinase), also known as CTK, this protein has amino acid sequence similarity to Csk tyrosine kinase and has the structural features of the CSK subfamily: SRC homology SH2 and SH3 domains, a catalytic domain, a unique N terminus, lack of myristylation signals, lack of a negative regulatory phosphorylation site, and lack of an autophosphorylation site. This protein is thought to play a significant role in the signal transduction of hematopoietic cells. It is able to phosphorylate and inactivate Src family kinases, and may play an inhibitory role in the control of T-cell proliferation. This protein might be involved in signaling in some cases of breast cancer.

Maternal embryonic leucine-zipper kinase (MELK) is a key regulator of survival of stemlike GBM cells in vitro. MELK expression is increased in breast cancer tissue and this increase is also associated with poor patient survival, as predicted for a candidate oncogene.

MER (c-mer proto-oncogene tyrosine kinase) is a member of the MER/AXL/TYRO3 receptor kinase family and encodes a transmembrane protein with two fibronectin type-III domains, two Ig-like C2-type (immunoglobulin-like) domains, and one tyrosine kinase domain. MER has been identified as a tyrosine kinase potentially involved in the development of glioblastomas. It is expressed at highest levels in ovary, prostate, lung and kidney. Gas6, a growth arrest specific gene, and the related anticoagulation factor Protein S have been identified as ligands for the UFO family of receptors. Mutations in this gene have been associated with disruption of the retinal pigment epithelium (RPE) phagocytosis pathway and onset of autosomal recessive retinitis pigmentosa (RP).

Metadherin (Metastasis adhesion protein), also known as MTDH, LYsine-RIch CEACAM1 co-isolated (LYRIC), is a novel protein that localizes with the tight junction proteins ZO-1 and occludin in polarized epithelial cells. At the tight junction, it acts not as a structural component, but is rather recruited during the maturation of the tight junction complex. Metadherin is overexpressed in breast cancer tissue and breast tumor xenografts, while much lower levels are expressed in normal breast tissue. Metadherin binds to lung vasculature, one of the four common sites of breast cancer metastasis, through a C-terminal segment in the extracellular domain; blocking this lung-homing domain with antibodies or inhibiting metadherin with siRNA has been reported to inhibit breast cancer metastasis.

DNA-mismatch repair (MMR), a conserved process that involves correcting errors made during DNA synthesis, is crucial to the maintenance of genomic integrity. Lack of a functional DNA-mismatch repair pathway is a common characteristic of several different types of human cancers, either due to an MMR gene mutation or promoter-methylation gene silencing. MLH1 is a human homolog of the E. coli DNA mismatch repair gene mutL, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in hereditary nonpolyposis colon cancer (HNPCC). MLH1 is an integral part of the protein complex responsible for mismatch repair expressed in lymphocytes, heart, colon, breast, lung, spleen, testis, prostate, thyroid and gall bladder, and is methylated in several ovarian tumors. Loss of MLH1 protein expression is associated with a mutated phenotype, microsatellite instability and a predisposition to cancer. In hereditary nonpolyposis colorectal cancer (HNPCC), an autosomal dominant inherited cancer syndrome that signifies a high risk of colorectal and various other types of cancer, the MLH1 gene exhibits a pathogenic mutation. Inactivation of the MLH1 gene causes genome instability and predisposition to cancer. MLH1 also plays a role in meiotic recombination.

Myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila). Eukaryotic RNA polymerase II mediates the synthesis of mature and functional messenger RNA. This is a multistep process, called the transcription cycle,that includes five stages: preinitiation, promoter, clearance, elongation and termination. Elongation is thought to be a critical stage for the regulation of gene expression. ELL (11-19 lysine-rich leukemia protein, also designated MEN) functions as an RNA polymerase II elongation factor that increases the rateof transcription by suppressing transient pausing by RNA polymerase II. Also, ELL is thought to regulate cellular proliferation. ELL is abundantly expressed in peripheral blood leukocytes, skeletal muscle, placenta and testis, and has lower expression in spleen, thymus, heart, brain, lung, kidney, liver and ovary.The gene encoding human ELL, which maps to chromosome 19p13.1, is one of several genes which undergo translocation with the MLL gene on chromo-some 11q23 in acute myeloid leukemia. MLL (myeloid/lymphoid leukemia,also designated ALL-1 and HRX) is a 430 kDa protein that regulates embryonal and hematopoietic development.

Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP’s are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. This gene encodes an enzyme which degrades fibronectin, laminin, collagens III, IV, IX, and X, and cartilage proteoglycans. The enzyme is thought to be involved in wound repair, progression of atherosclerosis, and tumor initiation. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3.

Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP’s are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The enzyme encoded by this gene degrades type IV and V collagens. Studies in rhesus monkeys suggest that the enzyme is involved in IL-8-induced mobilization of hematopoietic progenitor cells from bone marrow, and murine studies suggest a role in tumor-associated tissue remodeling.

Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP’s are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The enzyme encoded by this gene degrades type IV and V collagens. Studies in rhesus monkeys suggest that the enzyme is involved in IL-8-induced mobilization of hematopoietic progenitor cells from bone marrow, and murine studies suggest a role in tumor-associated tissue remodeling.

Defects in MSH6 are a cause of hereditary non-polyposis colorectal cancer (HNPCC) (Lynch syndrome). HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early onset colorectal carcinoma (crc) and extra-colonic cancers of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the western world. MSH6 is central to mismatch DNA repair.

This gene encodes a protein similar to the MutS protein. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides, prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein of this gene combines with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene have been identified in individuals with hereditary nonpolyposis colon cancer (HNPCC) and endometrial cancer.

This gene encodes a protein similar to the MutS protein. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides, prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein of this gene combines with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene have been identified in individuals with hereditary nonpolyposis colon cancer (HNPCC) and endometrial cancer.

Drosophila,muscle segment (msh) homolog 1,homeo domain encoding gene,inhibiting MYOD1 expression,highly expressed in dental mesenchyme during critical bud stage,involved in epithelial-mesenchymal signaling in many organs,and in the pathogenesis of cleft lip and palate,interacting with MSX2 in mouse limb bud patterning .This gene encodes a member of the muscle segment homeobox gene family. The encoded protein functions as a transcriptional repressor during embryogenesis through interactions with components of the core transcription complex and other homeoproteins. It may also have roles in limb-pattern formation, craniofacial development, particularly odontogenesis, and tumor growth inhibition.Tissue specificity: Expressed in the developing nail bed mesenchyme.

The protein encoded by this gene catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co-substrate for homocysteine remethylation to methionine. Genetic variation in this gene influences susceptibility to occlusive vascular disease, neural tube defects, colon cancer and acute leukemia, and mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.

The protein encoded by this gene is a multifunctional, nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. It functions as a transcription factor that regulates transcription of specific target genes. Mutations, overexpression, rearrangement and translocation of this gene have been associated with a variety of hematopoietic tumors, leukemias and lymphomas, including Burkitt lymphoma. There is evidence to show that alternative translation initiations from an upstream, in-frame non-AUG (CUG) and a downstream AUG start site result in the production of two isoforms with distinct N-termini. The synthesis of non-AUG initiated protein is suppressed in Burkitt’s lymphomas, suggesting its importance in the normal function of this gene. (provided by RefSeq).

NAC1 or nuclear accumbens-1 is a nuclear factor that belongs to the POZ/BTB (Pox virus and zinc finger/bric-a-brac tramtrack broad complex) domain family. Also known as BTBD14B, it was originally identified in a unique neuronal forebrain structure responsible for reward motivation and addictive behaviors . NAC1 recruits HDAC3 and HDAC4 to transcriptionally repress gene expression in neuronal cells (3) and specifically co-represses other POZ/BTB proteins in the central nervous system . NAC1 is upregulated in several tumor types, including breast, renal cell, and hepatocellular carcinoma, as well as high grade ovarian serous carcinoma, where it has long been suspected as a chemoresistance gene . The chemoresistance mechanism reportedly occurs through NAC1 negative regulation of the GADD45 pathway . NAC1 has also been described as part of the extended transcriptional network in pluripotent cells that involves Oct-4, Sox2, Nanog, Sall1, KLF4 and Sall4 . Tissue specificity: Overexpressed in several types of carcinomas including ovarian serous carcinomas. Expression levels positively correlate with tumor recurrence in ovarian serous carcinomas, and intense immunoreactivity in primary ovarian tumors predicts early recurrence. Up-regulated in ovarian carcinomas after chemotherapy, suggesting a role in development of chemotherapy resistance in ovarian cancer.

Nkx3.1 is a transcription factor that may play an important role in regulating proliferation of glandular epithelium and in the formation of ducts in the prostate. It has been thought to be one of the target genes of the 8p21 loss of heterozygosity, common in prostate cancer. But neither disruption of the coding region of the gene, nor mutations have been found in prostate cancer.

non-metastatic cells 1,protein,with a nm23 nucleoside diphosphate kinase gene family,involved in the phosphorylation of nucleoside diphosphates,with a reduced expression in tumor progression to the metastatic phenotype,mutated in agressive neuroblastoma,expressed in lung carcinoma cell lines not in normal lung,pyrimidine biosynthetic pathway. Involved in cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. Required for neural development including neural patterning and cell fate determination. Has tumor metastasis-suppressive capacity.Tissue specificity: Isoform 1 is expressed in heart, brain, placenta, lung, liver, skeletal muscle, pancreas, spleen and thymus. Expressed in lung carcinoma cell lines but not in normal lung tissues. Isoform 2 is ubiquitously expressed and its expression is also related to tumor differentiation. Isoform 3 is ubiquitously expressed.

Nitric oxide is a reactive free radical which acts as a biologic mediator in several processes, including neurotransmission and antimicrobial and antitumoral activities. This gene encodes a nitric oxide synthase which is expressed in liver and is inducible by a combination of lipopolysaccharide and certain cytokines. Three related pseudogenes are located within the Smith-Magenis syndrome region on chromosome 17.

This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase. This FAD-binding protein forms homodimers and reduces quinones to hydroquinones. This protein’s enzymatic activity prevents the one electron reduction of quinones that results in the production of radical species. Mutations in this gene have been associated with tardive dyskinesia (TD), an increased risk of hematotoxicity after exposure to benzene, and susceptibility to various forms of cancer. Altered expression of this protein has been seen in many tumors and is also associated with Alzheimer’s disease (AD). Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

This gene is a member of the NAD(P)H dehydrogenase (quinone) family and encodes a cytoplasmic 2-electron reductase. This FAD-binding protein forms homodimers and reduces quinones to hydroquinones. This protein’s enzymatic activity prevents the one electron reduction of quinones that results in the production of radical species. Mutations in this gene have been associated with tardive dyskinesia (TD), an increased risk of hematotoxicity after exposure to benzene, and susceptibility to various forms of cancer. Altered expression of this protein has been seen in many tumors and is also associated with Alzheimer’s disease (AD). Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

NTRK3 (neurotrophic tyrosine kinase, receptor, type 3), it is a member of the neurotrophic tyrosine receptor kinase (NTRK) family and plays an important role in the development and maintenance of neural tissues. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation and may play a role in the development of proprioceptive neurons that sense body position. Mutations in this gene have been associated with medulloblastomas, secretory breast carcinomas and other cancers.

NTRK3 (neurotrophic tyrosine kinase, receptor, type 3), it is a member of the neurotrophic tyrosine receptor kinase (NTRK) family and plays an important role in the development and maintenance of neural tissues. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation and may play a role in the development of proprioceptive neurons that sense body position. Mutations in this gene have been associated with medulloblastomas, secretory breast carcinomas and other cancers.

Nucleophosmin (NPM), also named B23 or NO38, is a major nucleolar protein which is 20 times more abundant in tumor or proliferating cells than in normal resting cells. NPM has been implicated in several distinct cellular functions, including assembly and transport of ribosomes, cytoplasmic/nuclear trafficking, regulation of DNA polymerase alpha activity, centrosome duplication and molecular chaperoning activities. The NPM is also known for its fusion with the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase. The NPM portion contributes to transformation by providing a dimerization domain, which results in activation of the fused kinase.

Oct4: octamer-binding transcription factor-4 (Oct-4, Otf-4) and Oct-3/4, also known as POU5F1(POU class 5 homeobox 1), octamerbinding transcription factor-3 (Oct-3, Otf-3), modulates embryonic stem (ES) cell populations by influencing lineage commitment. Entrez Protein NP_002692. Oct-3/4 sustains stem-cell selfrenewal and differentiation pathways. Transcription factors containing the POU homeodomain regulate tissue-specific gene expression in lymphoid and pituitary differentiation and in early mammalian development. Oct-3/4 is capable of inducing rapid proliferation and tumorigenic properties of ES cells through activation of the UTF1 gene. In humans, two Oct-3/4 isoforms contribute to influencing the undifferentiated phenotype of ES cells. Oct-3/4 pseudogenes localizing to human chromosomes 10 and 8 are reported to be transcribed in certain cancer cell lines and tissues.

This gene encodes a transcription factor containing a POU homeodomain. This transcription factor plays a role in embryonic development, especially during early embryogenesis, and it is necessary for embryonic stem cell pluripotency. A translocation of this gene with the Ewing’s sarcoma gene, t(6;22)(p21;q12), has been linked to tumor formation. Alternative splicing, as well as usage of alternative translation initiation codons, results in multiple isoforms, one of which initiates at a non-AUG (CUG) start codon. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12. (provided by RefSeq).Tissue specificity: Expressed in developing brain. Highest levels found in specific cell layers of the cortex, the olfactory bulb, the hippocampus and the cerebellum. Low levels of expression in adult tissues.

This gene encodes a transcription factor containing a POU homeodomain. This transcription factor plays a role in embryonic development, especially during early embryogenesis, and it is necessary for embryonic stem cell pluripotency. A translocation of this gene with the Ewing’s sarcoma gene, t(6;22)(p21;q12), has been linked to tumor formation. Alternative splicing, as well as usage of alternative translation initiation codons, results in multiple isoforms, one of which initiates at a non-AUG (CUG) start codon. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12. (provided by RefSeq).Tissue specificity: Expressed in developing brain. Highest levels found in specific cell layers of the cortex, the olfactory bulb, the hippocampus and the cerebellum. Low levels of expression in adult tissues.

This gene encodes a basic helix-loop-helix transcription factor which is expressed in oligodendroglial tumors of the brain. The protein is an essential regulator of ventral neuroectodermal progenitor cell fate. The gene is involved in a chromosomal translocation t(14;21)(q11.2;q22) associated with T-cell acute lymphoblastic leukemia. Its chromosomal location is within a region of chromosome 21 which has been suggested to play a role in learning deficits associated with Down syndrome. Tissue specificity: Expressed in the brain, in oligodendrocytes. Strongly expressed in oligodendrogliomas, while expression is weak to moderate in astrocytomas. Expression in glioblastomas highly variable.

p16 (cyclin-dependent kinase inhibitor 2A, INK4a) is a tumor suppressor protein. It is a specific inhibitor of Cdk 4 / Cdk 6, and a tumor suppressor involved in the pathogenesis of a variety of malignancies. Recent analyses of the p16 INK4a gene revealed homozygous deletions, nonsense, missense, or frameshift mutations in several human cancers. Although the frequency of p16 INK4a abnormalities is higher in tumor derived cell lines than in unselected primary tumors, significant subsets of clinical cases with aberrant p16 INK4a gene have been reported among melanomas, gliomas, esophageal, pancreatic, lung, and urinary bladder carcinomas, and some types of leukemia.

The progression of cells through the cell cycle is regulated by a family of protein kinases known as cyclin-dependent kinases (Cdks). The sequential activation of individual members of this family and their consequent phosphorylation of critical substrates promotes orderly progression through the cell cycle. The cyclins function as differentially expressed positive regulators of Cdks. Negative regulators of the cycle include the p53-inducible 21 kDa WAF1/Cip1 protein designated p21, Kip1 p27 and p16. The complexes formed by Cdk4 and the D-type cyclins have been strongly implicated in the control of cell proliferation during the G1 phase. It has recently been shown that p16 binds to Cdk4 and inhibits the catalytic activity of the Cdk4/cyclin D complex. Moreover, the gene encoding p16 exhibits a high frequency of homozygous deletions and point mutations in established human tumor cell lines.

The progression of cells through the cell cycle is regulated by a family of protein kinases known as cyclin-dependent kinases (Cdks). The sequential activation of individual members of this family and their consequent phosphorylation of critical substrates promotes orderly progression through the cell cycle. The cyclins function as differentially expressed positive regulators of Cdks. Negative regulators of the cycle include the p53-inducible 21 kDa WAF1/Cip1 protein designated p21, Kip1 p27 and p16. The complexes formed by Cdk4 and the D-type cyclins have been strongly implicated in the control of cell proliferation during the G1 phase. It has recently been shown that p16 binds to Cdk4 and inhibits the catalytic activity of the Cdk4/cyclin D complex. Moreover, the gene encoding p16 exhibits a high frequency of homozygous deletions and point mutations in established human tumor cell lines.

Mitogen-activated protein kinases (MAPKs) are a widely conserved family of serine/threonine protein kinases involved in many cellular programs such as cell proliferation, differentiation, motility, and death. The p44/42 MAPK (Erk1/2) signaling pathway can be activated in response to a diverse range of extracellular stimuli including mitogens, growth factors, and cytokines and is an important target in the diagnosis and treatment of cancer. Upon stimulation, a sequential three-part protein kinase cascade is initiated, consisting of a MAP kinase kinase kinase (MAPKKK or MAP3K), a MAP kinase kinase (MAPKK or MAP2K), and a MAP kinase (MAPK). Multiple p44/42 MAP3Ks have been identified, including members of the Raf family as well as Mos and Tpl2/Cot. MEK1 and MEK2 are the primary MAPKKs in this pathway. MEK1 and MEK2 activate p44 and p42 through phosphorylation of activation loop residues Thr202/Tyr204 and Thr185/Tyr187, respectively. Several downstream targets of p44/42 have been identified, including p90RSK and the transcription factor Elk-1. p44/42 are negatively regulated by a family of dual-specificity (Thr/Tyr) MAPK phosphatases, known as DUSPs or MKPs, along with MEK inhibitors such as U0126 and PD98059.

p53 responds to diverse cellular stresses to regulate target genes that induce cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. p53 protein is expressed at low level in normal cells and at a high level in a variety of transformed cell lines, where it's believed to contribute to transformation and malignancy. p53 is a DNA-binding protein containing transcription activation, DNA-binding, and oligomerization domains. It is postulated to bind to a p53-binding site and activate expression of downstream genes that inhibit growth and/or invasion, and thus function as a tumor suppressor. Mutants of p53 that frequently occur in a number of different human cancers fail to bind the consensus DNA binding site, and hence cause the loss of tumor suppressor activity. Alterations of this gene occur not only as somatic mutations in human malignancies, but also as germline mutations in some cancer-prone families with Li-Fraumeni syndrome. Multiple p53 variants due to alternative promoters and multiple alternative splicing have been found. These variants encode distinct isoforms, which can regulate p53 transcriptional activity.

The p63 gene is a homologue of the p53 tumor suppressor gene. Like p53, p63 contains a transactivation (TA) domain induce the transcription of target genes, a DNA binding domain, and an oligomerization domain (OD), used to form tetramers. In contrast to p53, the p63 gene encodes for at least six major isotypes. Three isotypes (TAp63α, TAp63β, and TAp63γ) contain the transactivating (TA) domain and are able to transactivate p53 report genes and induce apoptosis. In contrast, the other three isotypes (ΔNp63α, ΔNp63β, ΔNp63γ) are transcribed from an internal promoter localized within intron3, lack the TA domain, and act as dominant-negatives to suppress transactivation by both p53 and TAp63 isotypes. p63 is highly expressed in the basal cells of the epithelium significant for proper limb outgrowth and morphogenesis.4 In differentiating tissues, p63 is crucial for maintaining the stem cell identity of the basal cells, and is indispensable for correct development of the skin as well as the limb. p63-deficient mice lack all squamous epithelia and their derivatives, including hair, whiskers, teeth, as well as mammary, lacrimal, and salivary glands.Tissue specificity: Widely expressed, notably in heart, kidney, placenta, prostate, skeletal muscle, testis and thymus, although the precise isoform varies according to tissue type. Progenitor cell layers of skin, breast, eye and prostate express high levels of DeltaN-type isoforms. Isoform 10 is predominantly expressed in skin squamous cell carcinomas, but not in normal skin tissues.

Prostate apoptosis response 4 (Par4) is a 38kD protein originally identified as the product of a gene that is upregulated in prostate tumor cells undergoing apoptosis. It is a leucine zipper and death domain containing protein whose levels increase in neurons undergoing apoptosis as a result of trophic factor withdrawal or exposure to oxidative and metabolic insults. Par4 levels are reported to be increased in their lumbar spinal cord specimens further suggesting a role in neuronal degeneration. The tumor suppressor WT1 represses and activates transcription. The loss and/or imbalance of the dual transcriptional activity of WT1 may contribute to Wilms tumor. Par4 is a WT1 interacting protein that also functions as a transcriptional repressor.

This gene encodes a chromatin-associated enzyme, poly(ADP-ribosyl)transferase, which modifies various nuclear proteins by poly(ADP-ribosyl)ation. The modification is dependent on DNA and is involved in the regulation of various important cellular processes such as differentiation, proliferation, and tumor transformation and also in the regulation of the molecular events involved in the recovery of cell from DNA damage. In addition, this enzyme may be the site of mutation in Fanconi anemia, and may participate in the pathophysiology of type I diabetes.

This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. The paired box 4 gene is involved in pancreatic islet development and mouse studies have demonstrated a role for this gene in differentiation of insulin-producing beta cells.

This gene encodes a member of the paired box (PAX) family of transcription factors. Members of this gene family typically encode proteins that contain a paired box domain, an octapeptide, and a paired-type homeodomain. This nuclear protein is involved in thyroid follicular cell development and expression of thyroid-specific genes. Mutations in this gene have been associated with thyroid dysgenesis, thyroid follicular carcinomas and atypical follicular thyroid adenomas.Tissue specificity: Expressed in the excretory system, thyroid gland and Wilms tumors.ABCAM: This protein is a member of the paired box (PAX) family of transcription factors, typically containing a paired box domain, an octapeptide, and a paired-type homeodomain. This family plays critical roles during fetal development and cancer growth. The specific function of the PAX8 is unknown but it may involve kidney cell differentiation, thyroid development, or thyroid dysgenesis. Alternative splicing in the gene by inclusion or exclusion of exons 7 and/or 8 has produced several known products but the biological significance of the variants is unknown. Several other splice variants have been proposed but the full nature of these products has not been described. Pax8 is also a marker of otic progenitor cells.

Prohibitin is an evolutionarily conserved gene that is ubiquitously expressed. It is thought to be a negative regulator of cell proliferation and may be a tumor suppressor. Mutations in PHB have been linked to sporadic breast cancer. Prohibitin is expressed as two transcripts with varying lengths of 3′ untranslated region. The longer transcript is present at higher levels in proliferating tissues and cells, suggesting that this longer 3′ untranslated region may function as a trans-acting regulatory RNA.

Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers.

Pirh 2 (P53 induced RING-H2 protein), also known as RCHY1, it forms dimers through its N- and C-terminus in cells. The Pirh2 has ubiquitin-protein ligase activity and it binds with p53 and promotes the ubiquitin-mediated proteosomal degradation of p53. The Pirh2 is oncogenic because loss of p53 function contributes directly to malignant tumor development. Pirh2 expression decreases the level of p53, and a decrease of endogenous Pirh2 expression increases p53 levels. Pirh2 is therefore considered, together with MDM2, to act as a negative regulator of p53 function.

PLK1 is critical for the initiation of centrosome maturation. Polo-like kinases (PLKs) are a family of four serine/threonine protein kinases that are critical regulators of cell cycle progression, mitosis, cytokinesis, and the DNA damage response. PLK1, -2 and -3 are ubiquitously expressed, whereas PLK4 is restricted to a few tissues including the testes and the thymus. The mRNA and protein expression of PLK1, -2 and -4 are coordinately regulated during cell cycle progression, but PLK3 levels are independent of the other three family members. Furthermore, PLK3 is a much more stable protein than PLK1, -2 or -4. PLK1 is the most well characterized member of this family and strongly promotes the progression of cells through mitosis. During the various stages of mitosis PLK1 localizes to the centrosomes, kinetochores and central spindle. PLKs are dysregulated in a variety of human cancers. PLK1 overexpression correlates with cellular proliferation and poor prognosis. PLK2 and PLK3 are involved in checkpoint-mediated cell cycle arrest to ensure genetic stability. Loss-of-function mutations in these enzymes can lead to oncogenic transformation.

Implicated in a number of cellular processes, including proliferation, differentiation, caspase-dependent and caspase-independent apoptosis, suppression of transformation (tumor suppressor),inhibition of protein phosphatase 2A, regulation of mRNA trafficking and stability in association with ELAVL1, and inhibition of acetyltransferases as part of the INHAT (inhibitor of histone acetyltransferases) complex. Plays a role in E4F1-mediated transcriptional repression.

PPARG: peroxisome proliferator-activated receptor gamma. This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte differentiation. Additionally, PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis and cancer. Alternatively spliced transcript variants that encode different isoforms have been described.

The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase dephosphorylates, and negatively regulates the activities of, MAP kinases and MAP kinase kinases. It has been shown to inhibit the activation of p38 and JNK kinase cascades induced by environmental stresses. This phosphatase can also dephosphorylate cyclin-dependent kinases, and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to activate the expression of the tumor suppressor gene TP53/p53, which leads to G2/M cell cycle arrest and apoptosis. Three alternatively spliced transcript variants encoding distinct isoforms have been described.

PR(progesterone receptor), with 933-amino acid protein (about 110kDa), a member of the steroid receptor superfamily, mediates the physiologic effects of progesterone, PR is mediated by two functionally different isoforms of the progesterone receptor, the full length PR-B and the short form PR-A. The PR-A and PR-B proteins are 94 kDa and 114 kDa respectively. That are equimolar in the normal breast but dysregulated in advanced disease. PR is prognostic markers in breast cancers irrespective of the patient’s progestational status Human progesterone.

Kallikrein-related peptidase 3.Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. Its protein product is a protease present in seminal plasma. It is thought to function normally in the liquefaction of seminal coagulum, presumably by hydrolysis of the high molecular mass seminal vesicle protein. Serum level of this protein, called PSA in the clinical setting, is useful in the diagnosis and monitoring of prostatic carcinoma. Alternate splicing of this gene generates several transcript variants encoding different isoforms.

PTEN (phosphatase and tensin homolog) was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. This protein is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway.

PTK6 (protein tyrosine kinase 6, BRK or FLJ42088), with 451-amino acid protein (about 52kDa), encods a cytoplasmic nonreceptor protein kinase which may function as an intracellular signal transducer in epithelial tissues. Its presence in the nucleus appears to be linked to suppression of tumor progression. The encoded protein has been shown to undergo autophosphory-lation. Very high level in colon and high levels in small intestine and prostate, and low levels in some fetal tissues.  And Expressed at low level in some breast tumors, but not in normal breast. Also found in melanocytes, but not expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Overexpression of this gene in mammary epithelial cells leads to sensitization of the cells to epidermal growth factor and results in a partially transformed phenotype.

Receptor protein tyrosine kinases transduce extracellular signals across the cell membrane. A subgroup of these kinases lack detectable catalytic tyrosine kinase activity but retain roles in signal transduction. The protein encoded by this gene is a member of this subgroup of tyrosine kinases and may function as a cell adhesion molecule. This gene is thought to be expressed in colon carcinomas but not in normal colon, and therefore may be a marker for or may be involved in tumor progression. Four transcript variants encoding four different isoforms have been found for this gene.Tissue specificity: Highly expressed in lung, liver, pancreas, kidney, placenta and melanocytes. Weakly expressed in thyroid gland, ovary, brain, heart and skeletal muscle. Also expressed in erythroleukemia cells. But not expressed in colon.

The Rb protein regulates differentiation, apoptosis, and cell cycle control by coordinating the cell cycle at G1-S with transcriptional machinery. During G1, cyclin D-dependent kinase-mediated phosphorylation of Rb at Ser-795 marks the conversion of Rb from a transcriptionally repressive, hypophosphorylated state to an inactive, phosphorylated state, which may be sustained through mitosis by differential phosphorylation of up to 16 putative serine or threonine residues. Pediatric cancer retinoblastoma and the formation of other human tumors can be attributed to mutations in the retinoblastoma tumor suppressor gene(Rb).

RET (ret proto-oncogene) is a member of the cadherin superfamily and a receptor tyrosine kinase, which are cell-surface molecules that transduce signals for cell growth and differentiation. It can undergo oncogenic activation in vivo and in vitro by cytogenetic rearrangement. Ligands that bind the Ret receptor include the glial cell line-derived neurotropic factor (GDNF) and its congeners neurturin, persephin and artemin. Alterations in the corresponding Ret gene are associated with diseases including papillary thyroid carcinoma, multiple endocrine neoplasia (type 2A and 2B), familial medullary thyroid carcinoma and a congenital developmental disorder known as Hirschsprung disease. The Tyr905 residue located in the Ret kinase domain plays a crucial role in Ret catalytic and biological activity. Substitution of Phe for Tyr905 dramatically inhibits Ret autophosphorylation activity.

RET (ret proto-oncogene) is a member of the cadherin superfamily and a receptor tyrosine kinase, which are cell-surface molecules that transduce signals for cell growth and differentiation. It can undergo oncogenic activation in vivo and in vitro by cytogenetic rearrangement. Ligands that bind the Ret receptor include the glial cell line-derived neurotropic factor (GDNF) and its congeners neurturin, persephin and artemin. Alterations in the corresponding Ret gene are associated with diseases including papillary thyroid carcinoma, multiple endocrine neoplasia (type 2A and 2B), familial medullary thyroid carcinoma and a congenital developmental disorder known as Hirschsprung’s disease. The Tyr905 residue located in the Ret kinase domain plays a crucial role in Ret catalytic and biological activity. Substitution of Phe for Tyr905 dramatically inhibits Ret autophosphorylation activity.

This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 non-identical kinase catalytic domains and phosphorylates several residues of the S6 ribosomal protein. The kinase activity of this protein leads to an increase in protein synthesis and cell proliferation. Amplification of the region of DNA encoding this gene and overexpression of this kinase are seen in some breast cancer cell lines. Alternate translational start sites have been described and alternate transcriptional splice variants have been observed but have not been thoroughly characterized.

This gene encodes a member of the runt domain-containing family of transcription factors. A heterodimer of this protein and a beta subunit forms a complex that binds to the core DNA sequence 5′-PYGPYGGT-3′ found in a number of enhancers and promoters, and can either activate or suppress transcription. It also interacts with other transcription factors. It functions as a tumor suppressor, and the gene is frequently deleted or transcriptionally silenced in cancer. Multiple transcript variants encoding different isoforms have been found for this gene.

S100B (S100 calcium binding protein B) is a member of the S100 family of proteins containing 2 EF-hand calcium binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S-100 proteins and parvalbumin proteins are each expressed in neural tissues. In addition, S100B are present in a variety of other tissues, and calbindin is present in intestine and kidney. Parvalbumin B is found in many tumor tissues as well as in the organ of Corti. Calbindin, S-100 proteins and parvalbulmins have all been detected in leydig cells and the testis. These proteins are thought to play a role in hormone production and spermatogenesis. Chromosomal rearrangements and altered expression of this gene have been implicated in several neurological, neoplastic, and other types of diseases, including Alzheimer’s disease, Down’s syndrome, epilepsy, amyotrophic lateral sclerosis, melanoma, and type I diabetes.

Mammaglobin is a gene that is expressed almost exclusively in the normal breast epithelium and human breast cancer. It is a member of the secretoglobin gene family and forms a heterodimer with lipophilin B. It has been suggested that mammaglobin may be a useful marker for breast cancer clinical research. Studies investigating the detection of mRNA by RT PCR from circulating carcinoma cells in the peripheral blood of breast cancer patients have shown that mammaglobin is a highly specific marker and correlates with several prognostic factors, such as lymph node involvement.Tissue specificity: Mammary gland specific. Over-expressed in breast cancer.

The Sir2 protein in yeast is known to function in transcriptional silencing processes through the deacetylation of histones H3 and H4. The more recently described human homologue of Sir2, known as SIRT1, has been found to associate with the tumor suppressor protein p53.SIRT1 binds and deacetylates p53 with specificity for its C-terminal Lys382 residue in response to the upregulation of promyelocytic leukemia protein (PML) nuclear bodies or oncogenic Ras. The deacetylation of p53 SIRT1 has been shown to negatively regulate p53-mediated transcription, preventing cellular senescence and apoptosis induced by DNA damage and stress.SIRT1 has the closest homology to the yeast Sir2p and is widely expressed in fetal and adult tissues, with high expression in heart, brain and skeletal muscle and low expression in lung and placenta. SIRT1 regulates the p53-dependent DNA damage response pathway by binding to and deacetylating p53, specifically at Lysine 382.

Common mediator of signal transduction by TGF-beta (transforming growth factor) superfamily; SMAD4 is the common SMAD (co-SMAD). Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. May act as a tumor suppressor。Mutations or deletions in this gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome, and hereditary hemorrhagic telangiectasia syndrome.

Snail is a zinc-finger transcription factor that can repress E-cadherin transcription. Downregulation of E-cadherin is associated with epithelial-mesenchymal transition during embryonic development, a process also exploited by invasive cancer cells . Indeed, loss of E-cadherin expression is correlated with the invasive properties of some tumors and there is a considerable inverse correlation between Snail and E-cadherin mRNA levels in epithelial tumor cell lines . In addition, Snail blocks the cell cycle and confers resistance to cell death . Phosphorylation of Snail by GSK-3 and PAK1 regulates its stability, cellular localization and function .Tissue specificity: Expressed in a variety of tissues with the highest expression in kidney.

This gene encodes a member of the Snail family of C2H2-type zinc finger transcription factors. The encoded protein acts as a transcriptional repressor that binds to E-box motifs and is also likely to repress E-cadherin transcription in breast carcinoma. This protein is involved in epithelial-mesenchymal transitions and has antiapoptotic activity.The tumor suppressor protein p53 induces Slug expression in γ-irradiated cells; Slug protects damaged cells from apoptosis by repressing p53-induced transcription of the proapoptotic Bcl-2 family protein Puma. Mutations in this gene may be associated with sporatic cases of neural tube defects.

SNCG(also designated gamma-synuclein or breast cancer-specific protein 1),with 127-amino acid protein(about 14kDa), belongs to the synuclein family, which also includes alpha- and beta- synuclein.Three synucleins are located in the neuronal cytosol and enriched in presynaptic terminals,while SNCG is also expressed in many other non-neuronal tissues. SNCG is abnormally expressed in a high percentage of tumor tissues of diversified cancer types, including liver, esophagus, colon, gastric, lung, prostate, cervical, and breast cancer, but rarely expressed in tumor-matched nonneoplastic adjacent tissues. High levels of SNCG have been identified in advanced breast carcinomas suggesting a correlation between overexpression of SNCG and breast tumor development.

Steroid receptor RNA activator 1 (SRA), with 237-amino acid protein (about 27kDa), belongs to the growing family of functional non-coding RNAs. SRA was originally described as the first functional noncoding RNA able to specifically coactivate the activity of steroid receptors. Specifically, SRA exists as both an RNA transcript that forms a complex with steroid receptor coactivator-1 and as a stably expressed protein. Its expression is strongly up-regulated in many human tumors of the breast, uterus, and ovary, suggesting a potential role in pathogenesis. Although coactivation of steroid-dependent transcription by SRA is accompanied by a proliferative response, overexpression is not in itself sufficient to induce turmorigenesis.

Steroid receptor RNA activator 1 (SRA), with 237-amino acid protein (about 27kDa), belongs to the growing family of functional non-coding RNAs. SRA was originally described as the first functional noncoding RNA able to specifically coactivate the activity of steroid receptors. Specifically, SRA exists as both an RNA transcript that forms a complex with steroid receptor coactivator-1 and as a stably expressed protein. Its expression is strongly up-regulated in many human tumors of the breast, uterus, and ovary, suggesting a potential role in pathogenesis. Although coactivation of steroid-dependent transcription by SRA is accompanied by a proliferative response, overexpression is not in itself sufficient to induce turmorigenesis.

This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene.

SRC: v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian). This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene.

SRC: v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian). This gene is highly similar to the v-src gene of Rous sarcoma virus. This proto-oncogene may play a role in the regulation of embryonic development and cell growth. The protein encoded by this gene is a tyrosine-protein kinase whose activity can be inhibited by phosphorylation by c-SRC kinase. Mutations in this gene could be involved in the malignant progression of colon cancer. Two transcript variants encoding the same protein have been found for this gene.

The preproprotein encoded by this gene. Somatostatin is expressed throughout the body and inhibits the release of numerous secondary hormones by binding to high-affinity G-protein-coupled somatostatin receptors. This hormone is an important regulator of the endocrine system through its interactions with pituitary growth hormone, thyroid stimulating hormone, and most hormones of the gastrointestinal tract. Somatostatin also affects rates of neurotransmission in the central nervous system and proliferation of both normal and tumorigenic cells.

ST13 (suppression of tumorigenicity protein 13), also known as Hip (HSP70-interacting protein), is one of several co-chaperones that regulate activities of the HSP70 chaperone family. The homo-oligomeric protein Hip cooperates with HSP70 in protein folding by stabilizing the ADP-bound state of HSP70. Hip directly binds to the ATPase domain of HSP70 when it is converted to the ADP-bound state by proteins of the HSP40 family. By collaborating with other positive co-factors such as HSP40 and Hop, or competing with negative co-factors such as Bag1, Hip may facilitate the chaperone function of HSP70 in protein folding and repair, and in controlling the activity of regulatory proteins such as steroid receptors and various regulators of proliferation or apoptosis.

The Stat3 transcription factor is an important signaling molecule for many cytokines and growth-factor receptors and is required for murine fetal development . Stat3 is constitutively activated in a number of human tumors and possesses oncogenic potential and anti-apoptotic activities. Stat3 is activated by phosphorylation at Tyr705, which induces dimerization, nuclear translocation and DNA binding. Transcriptional activation seems to be regulated by phosphorylation at Ser727 through the MAPK or mTOR pathways. Stat3 isoform expression appears to reflect biological function as the relative expression levels of Stat3α (86 kDa) and Stat3β (79 kDa) depend on cell type, ligand exposure or cell maturation stage. It is notable that Stat3β lacks the serine phosphorylation site within the carboxy-terminal transcriptional activation domain.Tissue specificity: Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated by, and mediates the responses of many cell ligands, such as IL2, IL3, IL7 GM-CSF, erythropoietin, thrombopoietin, and different growth hormones. Activation of this protein in myeloma and lymphoma associated with a TEL/JAK2 gene fusion is independent of cell stimulus and has been shown to be essential for the tumorigenesis. The mouse counterpart of this gene is found to induce the expression of BCL2L1/BCL-X(L), which suggests the antiapoptotic function of this gene in cells.

Essential role in G1 cell cycle arrest. Phosphorylates and activates members of the AMPK-related subfamily of protein kinases. Tumor suppressor.serine/threonine kinase 11,with two alternatively spliced isoforms,expressed in all tissues,strongly homolog of Xenopus early embryonic kinase 1 (XEEK1),tumor suppressor gene in hamartomas syndrome and in left sided colon carcinogenesis,mutated in sporadic testicular cancer,malignant melanomas and laryngeal tumors,playing a minor role in the development of ovarian carcinoma.LKB1 is a potential target for atherosclerosis and cancer and is shown to be mutated in patients with Peutz-Jeghers cancer syndrome. Tissue specificity: Ubiquitously expressed. Strongest expression in testis and fetal liver.

Baculoviral IAP repeat-containing 5 (survivin). This gene is a member of the inhibitor of apoptosis (IAP) gene family, which encode negative regulatory proteins that prevent apoptotic cell death. IAP family members usually contain multiple baculovirus IAP repeat (BIR) domains, but this gene encodes proteins with only a single BIR domain. The encoded proteins also lack a C-terminus RING finger domain. Gene expression is high during fetal development and in most tumors yet low in adult tissues. Antisense transcripts are involved in the regulation of this gene’s expression. At least four transcript variants encoding distinct isoforms have been found for this gene, but the full-length natures of only three of them have been determined.

This zinc finger gene has been identified at the breakpoints of a recurrent chromosomal translocation reported in endometrial stromal sarcoma. Recombination of these breakpoints results in the fusion of this gene and JAZF1. The protein encoded by this gene contains a zinc finger domain in the C terminus of the coding region. (Provided by RefSeq) SUZ12 is overexpressed in several human tumors, including tumors of the colon, breast and liver.Tissue specificity: Overexpressed in breast and colon cancer.

This zinc finger gene has been identified at the breakpoints of a recurrent chromosomal translocation reported in endometrial stromal sarcoma. Recombination of these breakpoints results in the fusion of this gene and JAZF1. The protein encoded by this gene contains a zinc finger domain in the C terminus of the coding region. (Provided by RefSeq) SUZ12 is overexpressed in several human tumors, including tumors of the colon, breast and liver.Tissue specificity: Overexpressed in breast and colon cancer.

This gene encodes an epidermal growth factor-related protein that contains a cripto, FRL-1, and cryptic domain. The encoded protein is an extracellular, membrane-bound signaling protein that plays an essential role in embryonic development and tumor growth. Mutations in this gene are associated with forebrain defects.The cripto gene is expressed both in ES cells and during the early phases of embryo development, while in adults it is reactivated in a wide range of epithelial cancers. It could play a role in the determination of the epiblastic cells that subsequently give rise to the mesoderm.Tissue specificity: Preferentially expressed in gastric and colorectal carcinomas than in their normal counterparts.

TGF beta(transforming growth factor beta), with 390-amino acid protein (about 43 kDa), is a multifunctional peptide that controls proliferation, differentiation, and other functions in many cell types. In mammals, three isoforms of TGFbeta, that is, beta1, beta2,and beta3,are known. TGF beta is one of numerous inhibitory factors produced by cancer cells that regulate antitumor immunity. TGF beta1 takes part in the local response in the course of primary lung cancer and TGFbeta1 is thought to be implicated in breast cancer progression.TGFbeta1 also plays a critical role in the downregulation of microglial responses minimizing brain inflammation and thus avoiding exacerbation of brain damage.

This gene encodes a member of the transforming growth factor beta (TGFB) family of cytokines, which are multifunctional peptides that regulate proliferation, differentiation, adhesion, migration, and other functions in many cell types. Many cells have TGFB receptors, and the protein positively and negatively regulates many other growth factors. The secreted protein is cleaved into a latency-associated peptide (LAP) and a mature TGFB1 peptide, and is found in either a latent form composed of a TGFB1 homodimer, a LAP homodimer, and a latent TGFB1-binding protein, or in an active form composed of a TGFB1 homodimer. The mature peptide may also form heterodimers with other TGFB family members. This gene is frequently upregulated in tumor cells, and mutations in this gene result in Camurati-Engelmann disease

RET (ret proto-oncogene) is a member of the cadherin superfamily and a receptor tyrosine kinase, which are cell-surface molecules that transduce signals for cell growth and differentiation. It can undergo oncogenic activation in vivo and in vitro by cytogenetic rearrangement. Ligands that bind the Ret receptor include the glial cell line-derived neurotropic factor (GDNF) and its congeners neurturin, persephin and artemin. Alterations in the corresponding Ret gene are associated with diseases including papillary thyroid carcinoma, multiple endocrine neoplasia (type 2A and 2B), familial medullary thyroid carcinoma and a congenital developmental disorder known as Hirschsprung’s disease. The Tyr905 residue located in the Ret kinase domain plays a crucial role in Ret catalytic and biological activity. Substitution of Phe for Tyr905 dramatically inhibits Ret autophosphorylation activity.

This gene encodes a fast-twitch skeletal muscle protein, a member of the troponin I gene family, and a component of the troponin complex including troponin T, troponin C and troponin I subunits. The troponin complex, along with tropomyosin, is responsible for the calcium-dependent regulation of striated muscle contraction. Mouse studies show that this component is also present in vascular smooth muscle and may play a role in regulation of smooth muscle function. In addition to muscle tissues, this protein is found in corneal epithelium, cartilage where it is an inhibitor of angiogenesis to inhibit tumor growth and metastasis, and mammary gland where it functions as a co-activator of estrogen receptor-related receptor alpha. This protein also suppresses tumor growth in human ovarian carcinoma. Mutations in this gene cause myopathy and distal arthrogryposis type 2B. Alternatively spliced transcript variants have been found for this gene.