KEGG   PATHWAY: pcoq05215
Entry
pcoq05215                   Pathway                                
Name
Prostate cancer - Propithecus coquereli (Coquerel's sifaka)
Description
Prostate cancer constitutes a major health problem in Western countries. It is the most frequently diagnosed cancer among men and the second leading cause of male cancer deaths. The identification of key molecular alterations in prostate-cancer cells implicates carcinogen defenses (GSTP1), growth-factor-signaling pathways (NKX3.1, PTEN, and p27), and androgens (AR) as critical determinants of the phenotype of prostate-cancer cells. Glutathione S-transferases (GSTP1) are detoxifying enzymes. Cells of prostatic intraepithelial neoplasia, devoid of GSTP1, undergo genomic damage mediated by carcinogens. NKX3.1, PTEN, and p27 regulate the growth and survival of prostate cells in the normal prostate. Inadequate levels of PTEN and NKX3.1 lead to a reduction in p27 levels and to increased proliferation and decreased apoptosis. Androgen receptor (AR) is a transcription factor that is normally activated by its androgen ligand. During androgen withdrawal therapy, the AR signal transduction pathway also could be activated by amplification of the AR gene, by AR gene mutations, or by altered activity of AR coactivators. Through these mechanisms, tumor cells lead to the emergence of androgen-independent prostate cancer.
Class
Human Diseases; Cancer: specific types
Pathway map
pcoq05215  Prostate cancer
pcoq05215

Disease
H00024  Prostate cancer
Organism
Propithecus coquereli (Coquerel's sifaka) [GN:pcoq]
Gene
105804948  E2F1; transcription factor E2F1 [KO:K17454]
105805188  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
105805232  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105805288  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
105805737  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
105806045  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
105806240  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105806400  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
105806852  TMPRSS2; transmembrane protease serine 2 [KO:K09633] [EC:3.4.21.122]
105806898  ERG; transcriptional regulator ERG isoform X1 [KO:K09435]
105807166  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
105807372  [KO:K09047]
105807468  HSP90AB1; heat shock protein HSP 90-beta isoform X1 [KO:K04079]
105807545  KRAS; GTPase KRas [KO:K07827]
105807665  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
105808246  ETV5; ETS translocation variant 5 [KO:K15593]
105808352  IL1R2; interleukin-1 receptor type 2 [KO:K04387]
105808669  FGFR2; fibroblast growth factor receptor 2 [KO:K05093] [EC:2.7.10.1]
105808869  [KO:K04079]
105809025  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105809789  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
105809892  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
105809929  FOXO1; forkhead box protein O1 [KO:K07201]
105809996  AR; androgen receptor [KO:K08557]
105810199  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105810284  TCF7L1; transcription factor 7-like 1 [KO:K04490]
105810397  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105810591  NRAS; GTPase NRas [KO:K07828]
105810783  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105811104  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
105811149  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
105811965  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105811984  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
105812073  TGFA; protransforming growth factor alpha [KO:K08774]
105812249  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105812544  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
105812585  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
105812606  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105812777  [KO:K06643] [EC:2.3.2.27]
105813122  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
105813132  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
105813707  RB1; retinoblastoma-associated protein [KO:K06618]
105813943  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
105814042  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
105814517  SPINT1; kunitz-type protease inhibitor 1 isoform X1 [KO:K15619]
105814677  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
105815122  IGF1; insulin-like growth factor I [KO:K05459]
105815124  HSP90B1; endoplasmin [KO:K09487]
105815699  E2F2; transcription factor E2F2 [KO:K09389]
105815854  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
105816027  TCF7; transcription factor 7 isoform X1 [KO:K02620]
105816531  INS; insulin [KO:K04526]
105816561  HRAS; GTPase HRas isoform X1 [KO:K02833]
105816815  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
105816878  SRD5A2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:1.3.1.22]
105817322  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
105817331  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
105818006  SOS1; son of sevenless homolog 1 [KO:K03099]
105818191  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105818800  ZEB1; zinc finger E-box-binding homeobox 1 [KO:K09299]
105818935  EGF; pro-epidermal growth factor [KO:K04357]
105818969  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
105819002  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105819191  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105819395  TP53; cellular tumor antigen p53 [KO:K04451]
105819524  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
105819687  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
105819695  PLAT; tissue-type plasminogen activator [KO:K01343] [EC:3.4.21.68]
105820021  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
105820591  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105821530  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
105821582  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
105821880  INSRR; insulin receptor-related protein [KO:K05086] [EC:2.7.10.1]
105821904  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
105822157  [KO:K01394] [EC:3.4.24.17]
105822163  [KO:K05450]
105822164  [KO:K05450]
105822245  [KO:K01394] [EC:3.4.24.17]
105822702  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
105823104  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105823945  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
105824261  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
105824348  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
105824538  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
105824793  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
105824883  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
105824997  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
105825008  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
105825248  NKX3-1; homeobox protein Nkx-3.1 isoform X1 [KO:K09348]
105825335  CTNNB1; catenin beta-1 [KO:K02105]
105825510  PLAU; urokinase-type plasminogen activator [KO:K01348] [EC:3.4.21.73]
105825853  SOS2; son of sevenless homolog 2 [KO:K03099]
105826013  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
105826540  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
105826612  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105826847  [KO:K23790]
105827296  BAD; bcl2-associated agonist of cell death [KO:K02158]
105827383  RELA; transcription factor p65 isoform X1 [KO:K04735]
105827398  [KO:K23790]
105827423  CCND1; G1/S-specific cyclin-D1 isoform X1 [KO:K04503]
Compound
C00280  Androstenedione
C00410  Progesterone
C00535  Testosterone
C00735  Cortisol
C00762  Cortisone
C00951  Estradiol-17beta
C01227  Dehydroepiandrosterone
C03917  Dihydrotestosterone
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C07653  Flutamide
C16038  2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
Reference
PMID:12878745
  Authors
Nelson WG, De Marzo AM, Isaacs WB.
  Title
Prostate cancer.
  Journal
N Engl J Med 349:366-81 (2003)
DOI:10.1056/NEJMra021562
Reference
PMID:15724144
  Authors
Li L, Ittmann MM, Ayala G, Tsai MJ, Amato RJ, Wheeler TM, Miles BJ, Kadmon D, Thompson TC.
  Title
The emerging role of the PI3-K-Akt pathway in prostate cancer progression.
  Journal
Prostate Cancer Prostatic Dis 8:108-18 (2005)
DOI:10.1038/sj.pcan.4500776
Reference
PMID:16551847
  Authors
Pienta KJ, Bradley D.
  Title
Mechanisms underlying the development of androgen-independent prostate cancer.
  Journal
Clin Cancer Res 12:1665-71 (2006)
DOI:10.1158/1078-0432.CCR-06-0067
Reference
PMID:11900250
  Authors
Feldman BJ, Feldman D.
  Title
The development of androgen-independent prostate cancer.
  Journal
Nat Rev Cancer 1:34-45 (2001)
DOI:10.1038/35094009
Reference
PMID:15082523
  Authors
Heinlein CA, Chang C.
  Title
Androgen receptor in prostate cancer.
  Journal
Endocr Rev 25:276-308 (2004)
DOI:10.1210/er.2002-0032
Reference
PMID:9422516
  Authors
Koivisto P, Kolmer M, Visakorpi T, Kallioniemi OP.
  Title
Androgen receptor gene and hormonal therapy failure of prostate cancer.
  Journal
Am J Pathol 152:1-9 (1998)
Reference
PMID:10835690
  Authors
Zhao XY, Malloy PJ, Krishnan AV, Swami S, Navone NM, Peehl DM, Feldman D.
  Title
Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor.
  Journal
Nat Med 6:703-6 (2000)
DOI:10.1038/76287
Reference
PMID:10453277
  Authors
Macri E, Loda M.
  Title
Role of p27 in prostate carcinogenesis.
  Journal
Cancer Metastasis Rev 17:337-44 (1998)
DOI:10.1023/A:1006133620914
Reference
PMID:11750244
  Authors
Steers WD.
  Title
5alpha-reductase activity in the prostate.
  Journal
Urology 58:17-24; discussion 24 (2001)
DOI:10.1016/S0090-4295(01)01299-7
Reference
PMID:8069858
  Authors
Lin D, Meyer DJ, Ketterer B, Lang NP, Kadlubar FF.
  Title
Effects of human and rat glutathione S-transferases on the covalent DNA binding of the N-acetoxy derivatives of heterocyclic amine carcinogens in vitro: a possible mechanism of organ specificity in their carcinogenesis.
  Journal
Cancer Res 54:4920-6 (1994)
Reference
PMID:11527574
  Authors
Grimes CA, Jope RS.
  Title
The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling.
  Journal
Prog Neurobiol 65:391-426 (2001)
DOI:10.1016/S0301-0082(01)00011-9
Reference
PMID:21747944
  Authors
Leshem O, Madar S, Kogan-Sakin I, Kamer I, Goldstein I, Brosh R, Cohen Y, Jacob-Hirsch J, Ehrlich M, Ben-Sasson S, Goldfinger N, Loewenthal R, Gazit E, Rotter V, Berger R
  Title
TMPRSS2/ERG promotes epithelial to mesenchymal transition through the ZEB1/ZEB2 axis in a prostate cancer model.
  Journal
PLoS One 6:e21650 (2011)
DOI:10.1371/journal.pone.0021650
Reference
PMID:20478527
  Authors
Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, Wang X, Wu L, Li J, Hu M, Gong Y, Cheng H, Laxman B, Vellaichamy A, Shankar S, Li Y, Dhanasekaran SM, Morey R, Barrette T, Lonigro RJ, Tomlins SA, Varambally S, Qin ZS, Chinnaiyan AM
  Title
An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression.
  Journal
Cancer Cell 17:443-54 (2010)
DOI:10.1016/j.ccr.2010.03.018
Reference
PMID:19399032
  Authors
Squire JA
  Title
TMPRSS2-ERG and PTEN loss in prostate cancer.
  Journal
Nat Genet 41:509-10 (2009)
DOI:10.1038/ng0509-509
Reference
PMID:25915839
  Authors
Adamo P, Ladomery MR
  Title
The oncogene ERG: a key factor in prostate cancer.
  Journal
Oncogene 35:403-14 (2016)
DOI:10.1038/onc.2015.109
Reference
PMID:25485532
  Authors
Burdova A, Bouchal J, Tavandzis S, Kolar Z
  Title
TMPRSS2-ERG gene fusion in prostate cancer.
  Journal
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 158:502-10 (2014)
DOI:10.5507/bp.2014.065
Reference
PMID:18172298
  Authors
Helgeson BE, Tomlins SA, Shah N, Laxman B, Cao Q, Prensner JR, Cao X, Singla N, Montie JE, Varambally S, Mehra R, Chinnaiyan AM
  Title
Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 gene fusions in prostate cancer.
  Journal
Cancer Res 68:73-80 (2008)
DOI:10.1158/0008-5472.CAN-07-5352
Reference
PMID:28968951
  Authors
Kim H, Datta A, Talwar S, Saleem SN, Mondal D, Abdel-Mageed AB
  Title
Estradiol-ERbeta2 signaling axis confers growth and migration of CRPC cells through TMPRSS2-ETV5 gene fusion.
  Journal
Oncotarget 8:62820-62833 (2017)
DOI:10.18632/oncotarget.11355
Related
pathway
pcoq00140  Steroid hormone biosynthesis
pcoq04010  MAPK signaling pathway
pcoq04060  Cytokine-cytokine receptor interaction
pcoq04110  Cell cycle
pcoq04115  p53 signaling pathway
pcoq04151  PI3K-Akt signaling pathway
pcoq04210  Apoptosis
pcoq05202  Transcriptional misregulation in cancer
KO pathway
ko05215   

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