KEGG   PATHWAY: tfn05215
Entry
tfn05215                    Pathway                                
Name
Prostate cancer - Trachypithecus francoisi (Francois's langur)
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
tfn05215  Prostate cancer
tfn05215

Disease
H00024  Prostate cancer
Organism
Trachypithecus francoisi (Francois's langur) [GN:tfn]
Gene
117061979  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
117062119  TCF7L1; transcription factor 7-like 1 [KO:K04490]
117062284  IL1R2; interleukin-1 receptor type 2 isoform X1 [KO:K04387]
117062427  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
117063012  SRD5A2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:1.3.1.22]
117063258  RB1; retinoblastoma-associated protein [KO:K06618]
117065206  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
117065596  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
117065679  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
117065864  TCF7; transcription factor 7 isoform X1 [KO:K02620]
117066678  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
117066750  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
117067088  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
117067758  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
117068535  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
117068658  E2F1; LOW QUALITY PROTEIN: transcription factor E2F1 [KO:K17454]
117068860  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
117069667  SOS2; LOW QUALITY PROTEIN: son of sevenless homolog 2 [KO:K03099]
117069698  [KO:K04079]
117069810  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
117070145  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
117070473  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
117070849  SPINT1; kunitz-type protease inhibitor 1 isoform X1 [KO:K15619]
117071286  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
117071348  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
117072297  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
117072614  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
117072944  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
117073506  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
117073578  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
117074457  [KO:K04079]
117074634  NRAS; GTPase NRas [KO:K07828]
117075022  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
117075642  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
117076331  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117076490  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
117076784  INSRR; insulin receptor-related protein [KO:K05086] [EC:2.7.10.1]
117077749  AR; LOW QUALITY PROTEIN: androgen receptor [KO:K08557]
117078298  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
117078341  IKBKG; LOW QUALITY PROTEIN: NF-kappa-B essential modulator [KO:K07210]
117079029  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
117079895  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
117080013  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
117080612  BAD; bcl2-associated agonist of cell death [KO:K02158]
117081010  GSTP1; glutathione S-transferase P [KO:K23790]
117081143  INS; insulin [KO:K04526]
117081262  MMP3; stromelysin-1 [KO:K01394] [EC:3.4.24.17]
117081405  RELA; transcription factor p65 [KO:K04735]
117081518  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
117081688  HRAS; GTPase HRas isoform X1 [KO:K02833]
117082114  PLAU; urokinase-type plasminogen activator isoform X1 [KO:K01348] [EC:3.4.21.73]
117082707  [KO:K04079]
117082735  ZEB1; zinc finger E-box-binding homeobox 1 isoform X1 [KO:K09299]
117083269  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
117083296  [KO:K08557]
117083458  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
117083761  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
117083793  [KO:K06276] [EC:2.7.11.1]
117083853  ETV5; ETS translocation variant 5 [KO:K15593]
117083938  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
117084122  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
117084479  [KO:K04366] [EC:2.7.11.1]
117085606  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
117085710  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
117085762  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
117085785  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
117086074  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
117086783  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
117087134  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
117087288  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
117087606  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
117089519  HSP90B1; endoplasmin [KO:K09487]
117089531  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
117089769  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
117089961  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
117090495  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
117091652  [KO:K01351] [EC:3.4.21.77]
117091956  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
117092263  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
117092662  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
117093139  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
117093253  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
117093322  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
117093348  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
117093523  NKX3-1; homeobox protein Nkx-3.1 [KO:K09348]
117094598  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
117094867  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
117095617  PLAT; tissue-type plasminogen activator [KO:K01343] [EC:3.4.21.68]
117095630  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
117095774  ERG; transcriptional regulator ERG isoform X1 [KO:K09435]
117095813  TMPRSS2; transmembrane protease serine 2 isoform X1 [KO:K09633] [EC:3.4.21.122]
117096425  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
117096463  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
117096471  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
117096627  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
117097036  FOXO1; forkhead box protein O1 isoform X1 [KO:K07201]
117097726  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
117099006  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
117099723  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
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
tfn00140  Steroid hormone biosynthesis
tfn04010  MAPK signaling pathway
tfn04060  Cytokine-cytokine receptor interaction
tfn04110  Cell cycle
tfn04115  p53 signaling pathway
tfn04151  PI3K-Akt signaling pathway
tfn04210  Apoptosis
tfn05202  Transcriptional misregulation in cancer
KO pathway
ko05215   

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