Haynes Lab:Notebook/Synthetic Biology and Bioinformatics for Predictable Control of Therapeutic Gene2/2013/01/25

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(Gene Expression Round 2)
Current revision (04:36, 2 February 2013) (view source)
(Gene Expression Round 2)
 
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'''K562'''
'''K562'''
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''MAP Kinase Activity''
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#MAPK1: MiR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non-small-cell lung cancer through BIM down-regulation. Extracellular signal-regulated kinase 2 (ERK2) mediates phosphorylation and inactivation of nuclear interaction partner of anaplastic lymphoma kinase (NIPA) at G2/M.
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#NLK: Common variation in Nemo-like kinase is associated with risk of ovarian cancer.
''phosphotransferase activity, alcohol group as acceptor''
''phosphotransferase activity, alcohol group as acceptor''
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#EPHB2: Prognostic factor in colorectal cancer. Expression is significantly higher in NSCLC tissue than in control tissues, and were positively correlated with lymphatic metastasis. Expression has closed related to gennesis and progression of hepatoblastoma.
#EPHB2: Prognostic factor in colorectal cancer. Expression is significantly higher in NSCLC tissue than in control tissues, and were positively correlated with lymphatic metastasis. Expression has closed related to gennesis and progression of hepatoblastoma.
#PBK: PBK/TOPK (PDZ-binding kinase, T-LAK-cell-originated protein kinase) is a serine-threonine kinase that is overexpressed in a variety of tumor cells.
#PBK: PBK/TOPK (PDZ-binding kinase, T-LAK-cell-originated protein kinase) is a serine-threonine kinase that is overexpressed in a variety of tumor cells.
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#MAP4K1: Results indicate that uncleaved HPK1 is a positive regulator of vitamin D-induced differentiation in acute myeloid leukemia cells, but the cleaved HPK1 fragment inhibits differentiation. May function as a novel tumor suppressor and its loss plays a critical role in pancreatic cancer.
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#RIPK2: It is a potent activator of NF-kappaB and inducer of apoptosis in response to various stimuli.
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#FUK: The protein encoded by this gene belongs to the GHMP (galacto-, homoserine, mevalonate and phosphomevalonate) kinase family and catalyzes the phosphorylation of L-fucose to form beta-L-fucose 1-phosphate. This enzyme catalyzes the first step in the utilization of free L-fucose in glycoprotein and glycolipid synthesis. L-fucose may be important in mediating a number of cell-cell interactions such as blood group antigen recognition, inflammation, and metastatis.
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#LMTK3: LMTK3 is a therapeutic target in breast cancer.
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#PIP5KL1: Overexpression of PIP5KL1 suppresses cell proliferation and migration in human gastric cancer cells.
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#PRKAA1: Negative regulation of AMP-activated protein kinase (AMPK) activity by macrophage migration inhibitory factor (MIF) family members in non-small cell lung carcinomas. Data suggest that macrophage migration inhibitory factor (MIF) and d-dopachrome tautomerase (d-DT) act cooperatively to inhibit steady-state phosphorylation and activation of AMPK in LKB1 wild type and LKB1 mutant non-small cell lung carcinomas cells.
''Protein Kinase Activity''
''Protein Kinase Activity''
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#FGFR1OP: FGFR1 oncogene partner
#FGFR1OP: FGFR1 oncogene partner
#HIPK2: The encoded protein interacts with homeodomain transcription factors and many other transcription factors such as p53.
#HIPK2: The encoded protein interacts with homeodomain transcription factors and many other transcription factors such as p53.
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#CSNK2B: A dysregulation of CK2beta expression might contribute to epithelial-to-mesenchymal-transition induction during cancer progression. There was a positive correlation between the expressions of CK2alpha and CK2beta in laryngeal squamous cell carcinoma.
''structural molecule activity''
''structural molecule activity''
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''anion transmembrane transporter activity''
''anion transmembrane transporter activity''
#SLC4A7: associated with increased risk of breast cancer
#SLC4A7: associated with increased risk of breast cancer
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#APOL1: Alterations in ApoL1 function due to genetic, environmental, and lifestyle factors have been associated with African sleeping sickness, atherosclerosis, lipid disorders, obesity, schizophrenia, cancer, and chronic kidney disease (CKD). Similarly, ApoL1 may protect kidney cells against renal cell carcinoma (RCC).
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''protein tyrosine kinase activity''
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#NRP1: Neuropilin-1 is expressed by breast cancer stem-like cells and is linked to NF-κB activation and tumor sphere formation. High NRP1 is associated with acute myeloid and acute lymphoid leukemia.
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''kinase activity''
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#PIK3C3: PI 3-kinases p110 alpha- and beta- are ubiquitously expressed whilst p110 delta- expression is associated with leukocytes. Activating mutations in the p110alpha- subunit have recently been discovered in certain types of cancer cell.
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'''SK-N-SH'''
'''SK-N-SH'''
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''signaling receptor activity''
''signaling receptor activity''
#SFRP4: Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. (Wnt-signaling is highly involved in various cancers)
#SFRP4: Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. (Wnt-signaling is highly involved in various cancers)
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#CREB3L3: This gene encodes a member of the basic-leucine zipper family and the AMP-dependent transcription factor family. The encoded protein is localized to the endoplasmic reticulum and acts as a transcription factor activated by cyclic AMP stimulation. The encoded protein binds the cyclic AMP response element (CRE) and the box-B element and has been linked to acute inflammatory response, hepatocellular carcinoma, triglyceride metabolism, and hepcidin expression.
#CREB3L3: This gene encodes a member of the basic-leucine zipper family and the AMP-dependent transcription factor family. The encoded protein is localized to the endoplasmic reticulum and acts as a transcription factor activated by cyclic AMP stimulation. The encoded protein binds the cyclic AMP response element (CRE) and the box-B element and has been linked to acute inflammatory response, hepatocellular carcinoma, triglyceride metabolism, and hepcidin expression.
#RUNX3: It functions as a tumor suppressor, and the gene is frequently deleted or transcriptionally silenced in cancer.
#RUNX3: It functions as a tumor suppressor, and the gene is frequently deleted or transcriptionally silenced in cancer.
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#ARX: cancer/testis antigen 121
 
''G-protein coupled receptor activity''
''G-protein coupled receptor activity''
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#IL1B: inflammatory cytokines IL1B is shown to contribute to breast cancer development and metastasis
#IL1B: inflammatory cytokines IL1B is shown to contribute to breast cancer development and metastasis
#BMP4: Upregulation of bone morphogenetic protein 4 is associated with hepatocellular carcinoma.
#BMP4: Upregulation of bone morphogenetic protein 4 is associated with hepatocellular carcinoma.
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#TNFSF11: This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation.
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#TNFSF14: The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein has been shown to stimulate the proliferation of T cells, and trigger apoptosis of various tumor cells.
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#TNFSF9: This cytokine is expressed in carcinoma cell lines, and is thought to be involved in T cell-tumor cell interaction.
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#TNFSF15: The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. It can activate NF-kappaB and MAP kinases, and acts as an autocrine factor to induce apoptosis in endothelial cells. TNFSF15 is present prominently in the vasculature of normal ovary but diminishes in ovarian cancer as the disease progresses. Silencing TNFSF15 greatly facilitates angiogenesis and tumor growth, whereas systemic application of recombinant TNFSF15 inhibits angiogenesis and tumor growth.
''sequence-specific DNA binding transcription factor activity''
''sequence-specific DNA binding transcription factor activity''
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#CYP2A6: Cytochrome P450 2A6 (CYP2A6) is an enzyme responsible for the metabolism of nicotine and some tobacco-specific carcinogens (such as N-nitrosamines). CYP2A6 genetic variations are associated with the activity of the CYP2A6 enzyme, which affects smoking behavior and the rate at which some tobacco-specific carcinogens are metabolized, which in turn determines the incidence of lung cancer.  
#CYP2A6: Cytochrome P450 2A6 (CYP2A6) is an enzyme responsible for the metabolism of nicotine and some tobacco-specific carcinogens (such as N-nitrosamines). CYP2A6 genetic variations are associated with the activity of the CYP2A6 enzyme, which affects smoking behavior and the rate at which some tobacco-specific carcinogens are metabolized, which in turn determines the incidence of lung cancer.  
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Gene Expression Round 2

K562
MAP Kinase Activity

  1. MAPK1: MiR-494 is regulated by ERK1/2 and modulates TRAIL-induced apoptosis in non-small-cell lung cancer through BIM down-regulation. Extracellular signal-regulated kinase 2 (ERK2) mediates phosphorylation and inactivation of nuclear interaction partner of anaplastic lymphoma kinase (NIPA) at G2/M.
  2. NLK: Common variation in Nemo-like kinase is associated with risk of ovarian cancer.

phosphotransferase activity, alcohol group as acceptor

  1. MAP3K11: This kinase can directly phosphorylate, and activates IkappaB kinase alpha and beta, and is found to be involved in the transcription activity of NF-kappaB mediated by Rho family GTPases and CDC42. Incorrect regulation of NF-κB has been linked to cancer. lkappaB kinase participates in the metabolic pathway of pancreatic cancer, prostate cancer, chronic myeloid leukemia, acute myeloid leukemia, and small cell lung cancer.
  2. MAP2K6: This protein phosphorylates and activates p38 MAP kinase in response to inflammatory cytokines or environmental stress. As an essential component of p38 MAP kinase mediated signal transduction pathway, this gene is involved in many cellular processes such as stress induced cell cycle arrest, transcription activation and apoptosis. p38 activation results in cancer cell apoptosis
  3. N4BP2: The encoded protein can bind to both B-cell leukemia/lymphoma 3 (BCL-3) and neural precursor cell expressed, developmentally downregulated 4, (Nedd4) proteins.

structural molecule activity

  1. EPHB2: Prognostic factor in colorectal cancer. Expression is significantly higher in NSCLC tissue than in control tissues, and were positively correlated with lymphatic metastasis. Expression has closed related to gennesis and progression of hepatoblastoma.
  2. PBK: PBK/TOPK (PDZ-binding kinase, T-LAK-cell-originated protein kinase) is a serine-threonine kinase that is overexpressed in a variety of tumor cells.
  3. MAP4K1: Results indicate that uncleaved HPK1 is a positive regulator of vitamin D-induced differentiation in acute myeloid leukemia cells, but the cleaved HPK1 fragment inhibits differentiation. May function as a novel tumor suppressor and its loss plays a critical role in pancreatic cancer.
  4. RIPK2: It is a potent activator of NF-kappaB and inducer of apoptosis in response to various stimuli.
  5. FUK: The protein encoded by this gene belongs to the GHMP (galacto-, homoserine, mevalonate and phosphomevalonate) kinase family and catalyzes the phosphorylation of L-fucose to form beta-L-fucose 1-phosphate. This enzyme catalyzes the first step in the utilization of free L-fucose in glycoprotein and glycolipid synthesis. L-fucose may be important in mediating a number of cell-cell interactions such as blood group antigen recognition, inflammation, and metastatis.
  6. LMTK3: LMTK3 is a therapeutic target in breast cancer.
  7. PIP5KL1: Overexpression of PIP5KL1 suppresses cell proliferation and migration in human gastric cancer cells.
  8. PRKAA1: Negative regulation of AMP-activated protein kinase (AMPK) activity by macrophage migration inhibitory factor (MIF) family members in non-small cell lung carcinomas. Data suggest that macrophage migration inhibitory factor (MIF) and d-dopachrome tautomerase (d-DT) act cooperatively to inhibit steady-state phosphorylation and activation of AMPK in LKB1 wild type and LKB1 mutant non-small cell lung carcinomas cells.

Protein Kinase Activity

  1. ABL1: Activity of c-Abl protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene. The t(9;22) translocation results in the head-to-tail fusion of the BCR (MIM:151410) and ABL1 genes present in many cases of chronic myelogeneous leukemia.
  2. LMTK2: This protein interacts with several other proteins, such as Inhibitor-2 (Inh2), protein phosphatase-1 (PP1C), p35, and myosin VI.
  3. AKAP13: Alternative splicing of this gene results in multiple transcript variants encoding different isoforms containing c-terminal dbl oncogene homology (DH) and pleckstrin homology (PH) domains.
  4. NRG2: rough interaction with the ERBB family of receptors, this protein induces the growth and differentiation of epithelial, neuronal, glial, and other types of cells.
  5. PDGFRB: They have roles in the regulation of many biological processes including embryonic development, angiogenesis, cell proliferation and differentiation, and contribute to the pathophysiology of some diseases, including cancer. A translocation between chromosomes 5 and 12, that fuses this gene to that of the translocation, ETV6, leukemia gene, results in chronic myeloproliferative disorder with eosinophilia.
  6. MAPKAPK5: The protein encoded by this gene is a tumor suppressor and member of the serine/threonine kinase family.
  7. AATK: This gene is induced during apoptosis, and expression of this gene may be a necessary pre-requisite for the induction of growth arrest and/or apoptosis of myeloid precursor cells. This gene has been shown to produce neuronal differentiation in a neuroblastoma cell line.
  8. FES: This gene encodes the human cellular counterpart of a feline sarcoma retrovirus protein with transforming capabilities. Its chromosomal location has linked it to a specific translocation event identified in patients with acute promyelocytic leukemia.
  9. FGFR1OP: FGFR1 oncogene partner
  10. HIPK2: The encoded protein interacts with homeodomain transcription factors and many other transcription factors such as p53.
  11. CSNK2B: A dysregulation of CK2beta expression might contribute to epithelial-to-mesenchymal-transition induction during cancer progression. There was a positive correlation between the expressions of CK2alpha and CK2beta in laryngeal squamous cell carcinoma.

structural molecule activity

  1. RPL26L1: This gene encodes a protein that shares high sequence similarity with ribosomal protein L26 (involved in regulation of p53 - cancer involved)
  2. CHI3L1: This gene encodes a glycoprotein member of the glycosyl hydrolase 18 family. The protein lacks chitinase activity and is secreted by activated macrophages, chondrocytes, neutrophils and synovial cells. The protein is thought to play a role in the process of inflammation and tissue remodeling.
  3. CTNNB1: Mutations in this gene are a cause of colorectal cancer (CRC), pilomatrixoma (PTR), medulloblastoma (MDB), and ovarian cancer.

structural molecule activity

  1. COL4A2: This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. The C-terminal portion of the protein, known as canstatin, is an inhibitor of angiogenesis and tumor growth.
  2. FBLN2: This gene encodes an extracellular matrix protein, which belongs to the fibulin family. This protein binds various extracellular ligands and calcium. It may play a role during organ development, in particular, during the differentiation of heart, skeletal and neuronal structures. Tissue regeneration?

anion transmembrane transporter activity

  1. SLC4A7: associated with increased risk of breast cancer
  2. APOL1: Alterations in ApoL1 function due to genetic, environmental, and lifestyle factors have been associated with African sleeping sickness, atherosclerosis, lipid disorders, obesity, schizophrenia, cancer, and chronic kidney disease (CKD). Similarly, ApoL1 may protect kidney cells against renal cell carcinoma (RCC).

protein tyrosine kinase activity

  1. NRP1: Neuropilin-1 is expressed by breast cancer stem-like cells and is linked to NF-κB activation and tumor sphere formation. High NRP1 is associated with acute myeloid and acute lymphoid leukemia.

kinase activity

  1. PIK3C3: PI 3-kinases p110 alpha- and beta- are ubiquitously expressed whilst p110 delta- expression is associated with leukocytes. Activating mutations in the p110alpha- subunit have recently been discovered in certain types of cancer cell.


SK-N-SH

signaling receptor activity

  1. SFRP4: Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. (Wnt-signaling is highly involved in various cancers)
  2. TGFBR3: This locus encodes the transforming growth factor (TGF)-beta type III receptor. The encoded receptor is a membrane proteoglycan that often functions as a co-receptor with other TGF-beta receptor superfamily members. Ectodomain shedding produces soluble TGFBR3, which may inhibit TGFB signaling. Decreased expression of this receptor has been observed in various cancers.
  3. CHRNA3: Polymorphisms in this gene have been associated with an increased risk of smoking initiation and an increased susceptibility to lung cancer.
  4. EPBH4: Expression is significantly higher in NSCLC tissue than in control tissues, and were positively correlated with lymphatic metastasis. EphB4 plays an important role in the progression of papillary thyroid carcinoma by stimulating cell migration and EphB4 might be a potential therapeutic target in papillary thyroid carcinoma. EphB4 protein expression is significantly increased in non-small- cell lung cancer and corresponds to progression and severity of the disease. Expression has closed related to gennesis and progression of hepatoblastoma. Observed as being significantly related to tumor size and regional lymph nodes category.
  5. IL13RA1: cancer/testis antigen

signal transducer activity

  1. AXIN2: The Axin-related protein, Axin2, presumably plays an important role in the regulation of the stability of beta-catenin in the Wnt signaling pathway. Apparently, the deregulation of beta-catenin is an important event in the genesis of a number of malignancies. The AXIN2 gene has been mapped to 17q23-q24, a region that shows frequent loss of heterozygosity in breast cancer, neuroblastoma, and other tumors. Mutations in this gene have been associated with colorectal cancer with defective mismatch repair.
  2. MAP3K1: The protein encoded by this gene is a serine/threonine kinase and is part of some signal transduction cascades, including the ERK and JNK kinase pathways as well as the NF-kappa-B pathway. Incorrect regulation of NF-κB has been linked to cancer..

sequence-specific DNA binding

  1. HNF1B: mutations in this gene result in renal cysts and diabetes syndrome and noninsulin-dependent diabetes mellitus, and expression of this gene is altered in some types of cancer.
  2. IKZF1: This gene encodes a transcription factor that belongs to the family of zinc-finger DNA binding proteins associated with chromatin remodeling. The expression of this protein is restricted to the fetal and adult hemo-lymphopoietic system, and it functions as a regulator of lymphocyte differentiation. Overexpression of some dominant-negative isoforms have been associated with B-cell malignancies, such as acute lymphoblastic leukemia (ALL).
  3. TAL1: T-cell acute lymphocytic leukemia 1
  4. FEV: ETS oncogene family
  5. RXRG: This gene is expressed at significantly lower levels in non-small cell lung cancer cells.
  6. MSX1: 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.
  7. CREB3L3: This gene encodes a member of the basic-leucine zipper family and the AMP-dependent transcription factor family. The encoded protein is localized to the endoplasmic reticulum and acts as a transcription factor activated by cyclic AMP stimulation. The encoded protein binds the cyclic AMP response element (CRE) and the box-B element and has been linked to acute inflammatory response, hepatocellular carcinoma, triglyceride metabolism, and hepcidin expression.
  8. RUNX3: It functions as a tumor suppressor, and the gene is frequently deleted or transcriptionally silenced in cancer.

G-protein coupled receptor activity

  1. ADRA1B: Thus, this normal cellular gene is identified as a protooncogene.

sequence-specific DNA binding transcription factor activity

  1. CDKN2A: his ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, the E3 ubiquitin-protein ligase MDM2, 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.
  2. ST18: suppression of tumorigenicity 18 (breast carcinoma)
  3. WNT5A: The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene encodes a member of the WNT family that signals through both the canonical and non-canonical WNT pathways. This protein is a ligand for the seven transmembrane receptor frizzled-5 and the tyrosine kinase orphan receptor 2. This protein plays an essential role in regulating developmental pathways during embryogenesis. This protein may also play a role in oncogenesis.
  4. MECOM: This gene can undergo translocation with the AML1 gene, resulting in overexpression of this gene and the onset of leukemia.

transmembrane transporter activity

  1. SLC22A3: Role in prostate cancer pathogenesis.

growth factor activity

  1. KITLG: Linked to predisposing testicular germ cell cancer.
  2. IGF2: It is an imprinted gene, expressed only from the paternal allele, and epigenetic changes at this locus are associated with Wilms tumour, Beckwith-Wiedemann syndrome, rhabdomyosarcoma, and Silver-Russell syndrome.

receptor binding

  1. FGF4: The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This gene was identified by its oncogenic transforming activity. This gene and FGF3, another oncogenic growth factor, are located closely on chromosome 11. Co-amplification of both genes was found in various kinds of human tumors.
  2. IL1B: inflammatory cytokines IL1B is shown to contribute to breast cancer development and metastasis
  3. BMP4: Upregulation of bone morphogenetic protein 4 is associated with hepatocellular carcinoma.
  4. TNFSF11: This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation.
  5. TNFSF14: The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein has been shown to stimulate the proliferation of T cells, and trigger apoptosis of various tumor cells.
  6. TNFSF9: This cytokine is expressed in carcinoma cell lines, and is thought to be involved in T cell-tumor cell interaction.
  7. TNFSF15: The protein encoded by this gene is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. It can activate NF-kappaB and MAP kinases, and acts as an autocrine factor to induce apoptosis in endothelial cells. TNFSF15 is present prominently in the vasculature of normal ovary but diminishes in ovarian cancer as the disease progresses. Silencing TNFSF15 greatly facilitates angiogenesis and tumor growth, whereas systemic application of recombinant TNFSF15 inhibits angiogenesis and tumor growth.

sequence-specific DNA binding transcription factor activity

  1. MYCL1: v-myc myelocytomatosis viral oncogene homolog 1, lung carcinoma derived

transporter activity

  1. STEAP2: Increased transcriptional expression of the human gene is associated with prostate cancer progression.


oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen

  1. CYP2A6: Cytochrome P450 2A6 (CYP2A6) is an enzyme responsible for the metabolism of nicotine and some tobacco-specific carcinogens (such as N-nitrosamines). CYP2A6 genetic variations are associated with the activity of the CYP2A6 enzyme, which affects smoking behavior and the rate at which some tobacco-specific carcinogens are metabolized, which in turn determines the incidence of lung cancer.


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