KEGG   PATHWAY: rbb05215
Entry
rbb05215                    Pathway                                
Name
Prostate cancer - Rhinopithecus bieti (black snub-nosed monkey)
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
rbb05215  Prostate cancer
rbb05215

Disease
H00024  Prostate cancer
Organism
Rhinopithecus bieti (black snub-nosed monkey) [GN:rbb]
Gene
108512087  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
108512141  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
108512401  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
108512498  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108513636  SOS2; son of sevenless homolog 2 [KO:K03099]
108514072  MMP3; stromelysin-1 [KO:K01394] [EC:3.4.24.17]
108514115  FOXO1; forkhead box protein O1 [KO:K07201]
108514363  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
108514672  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
108515537  INSRR; insulin receptor-related protein isoform X1 [KO:K05086] [EC:2.7.10.1]
108515891  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
108515924  ZEB1; zinc finger E-box-binding homeobox 1 isoform X1 [KO:K09299]
108516053  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
108516633  SRD5A2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:1.3.1.22]
108516897  PLAU; urokinase-type plasminogen activator isoform X1 [KO:K01348] [EC:3.4.21.73]
108517986  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
108518709  GSTP1; glutathione S-transferase P [KO:K23790]
108518784  IKBKG; NF-kappa-B essential modulator [KO:K07210]
108518846  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
108518996  CREB3; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3 [KO:K09048]
108519245  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
108519636  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
108520463  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
108520474  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
108520869  SOS1; son of sevenless homolog 1 [KO:K03099]
108521880  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108522039  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
108522131  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
108522656  [KO:K08557]
108523426  SPINT1; kunitz-type protease inhibitor 1 isoform X1 [KO:K15619]
108523695  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
108523748  KRAS; GTPase KRas isoform X1 [KO:K07827]
108524092  IL1R2; interleukin-1 receptor type 2 isoform X1 [KO:K04387]
108524269  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
108524582  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
108525487  ETV5; ETS translocation variant 5 [KO:K15593]
108526412  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
108527540  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]
108527784  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
108528122  NRAS; GTPase NRas [KO:K07828]
108528336  CDKN1A; LOW QUALITY PROTEIN: cyclin-dependent kinase inhibitor 1 [KO:K06625]
108528445  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
108529019  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
108529562  TCF7; LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
108529768  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
108530144  [KO:K08557]
108530341  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
108530611  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
108530701  RB1; retinoblastoma-associated protein [KO:K06618]
108530908  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
108532047  PDGFRB; LOW QUALITY PROTEIN: platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
108532254  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
108532415  KLK3; LOW QUALITY PROTEIN: prostate-specific antigen [KO:K01351] [EC:3.4.21.77]
108532817  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
108532960  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
108533038  E2F1; LOW QUALITY PROTEIN: transcription factor E2F1 [KO:K17454]
108533326  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
108533442  HSP90AB1; LOW QUALITY PROTEIN: heat shock protein HSP 90-beta [KO:K04079]
108533750  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
108534276  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
108534725  TMPRSS2; transmembrane protease serine 2 isoform X1 [KO:K09633] [EC:3.4.21.122]
108534757  PDGFD; platelet-derived growth factor D [KO:K05450]
108535003  ERG; transcriptional regulator ERG isoform X1 [KO:K09435]
108535077  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
108535460  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
108535636  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
108535938  [KO:K06643] [EC:2.3.2.27]
108536070  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
108537061  [KO:K04079]
108537414  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
108537886  NKX3-1; homeobox protein Nkx-3.1 [KO:K09348]
108538320  CREBBP; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
108538448  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
108538668  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
108538745  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
108539069  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
108539226  INS; insulin isoform X1 [KO:K04526]
108539355  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108539366  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
108539896  CCNE2; LOW QUALITY PROTEIN: G1/S-specific cyclin-E2 [KO:K06626]
108540349  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
108540718  PLAT; tissue-type plasminogen activator [KO:K01343] [EC:3.4.21.68]
108540719  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
108541026  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
108541175  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
108541537  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
108541757  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
108542298  HSP90AA1; LOW QUALITY PROTEIN: heat shock protein HSP 90-alpha [KO:K04079]
108542315  PDGFA; LOW QUALITY PROTEIN: platelet-derived growth factor subunit A [KO:K04359]
108542456  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
108542557  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
108542618  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
108542734  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
108542809  TCF7L1; transcription factor 7-like 1 [KO:K04490]
108543134  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
108543519  RELA; transcription factor p65 [KO:K04735]
108543525  HRAS; GTPase HRas isoform X1 [KO:K02833]
108544251  HSP90B1; LOW QUALITY PROTEIN: endoplasmin [KO:K09487]
108544591  PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
rbb00140  Steroid hormone biosynthesis
rbb04010  MAPK signaling pathway
rbb04060  Cytokine-cytokine receptor interaction
rbb04110  Cell cycle
rbb04115  p53 signaling pathway
rbb04151  PI3K-Akt signaling pathway
rbb04210  Apoptosis
rbb05202  Transcriptional misregulation in cancer
KO pathway
ko05215   

DBGET integrated database retrieval system