KEGG   PATHWAY: oas05215
oas05215                    Pathway                                

Prostate cancer - Ovis aries (sheep)
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.
Human Diseases; Cancer: specific types
Pathway map
oas05215  Prostate cancer

Ovis aries (sheep) [GN:oas]
105607169  glutathione S-transferase P [KO:K23790] [EC:]
114116112  glutathione S-transferase P-like [KO:K23790] [EC:]
101120874  GSTP1; glutathione S-transferase P [KO:K23790] [EC:]
100127219  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
100216433  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:]
101109811  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
101107124  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
100144755  RB1; retinoblastoma-associated protein [KO:K06618]
101117526  E2F1; transcription factor E2F1 [KO:K17454]
105606975  E2F2; transcription factor E2F2 [KO:K09389]
101121809  E2F3; transcription factor E2F3 [KO:K06620]
101120216  TMPRSS2; transmembrane protease serine 2 [KO:K09633] [EC:3.4.21.-]
101110646  ERG; transcriptional regulator ERG isoform X1 [KO:K09435]
100302501  PLAU; urokinase-type plasminogen activator precursor [KO:K01348] [EC:]
101118332  PLAT; tissue-type plasminogen activator [KO:K01343] [EC:]
101118895  stromelysin-1 [KO:K01394] [EC:]
100192422  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:]
101115891  ZEB1; zinc finger E-box-binding homeobox 1 isoform X1 [KO:K09299]
101103308  IL1R2; interleukin-1 receptor type 2 [KO:K04387]
101111287  SPINT1; kunitz-type protease inhibitor 1 isoform X2 [KO:K15619]
101115418  ETV5; ETS translocation variant 5 isoform X1 [KO:K15593]
114110121  INS; insulin [KO:K04526]
114110564  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
443545  PDGFB; platelet-derived growth factor subunit B precursor [KO:K17386]
101117784  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
101112600  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
101106508  TGFA; protransforming growth factor alpha [KO:K08774]
443318  IGF1; insulin-like growth factor I precursor [KO:K05459]
101108266  INSRR; insulin receptor-related protein [KO:K05086] [EC:]
101106012  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:]
101122783  PDGFRB; LOW QUALITY PROTEIN: platelet-derived growth factor receptor beta [KO:K05089] [EC:]
780507  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:]
443548  FGFR2; fibroblast growth factor receptor 2 isoform X3 [KO:K05093] [EC:]
780479  EGFR; epidermal growth factor receptor [KO:K04361] [EC:]
780519  ERBB2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:]
443515  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:]
101109759  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:]
101110015  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
101117348  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:]
101123247  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101111546  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
101121455  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
101119351  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X2 [KO:K01110] [EC:]
101117211  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:]
101113199  NKX3-1; homeobox protein Nkx-3.1 [KO:K09348]
101118462  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:]
101119242  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
100294652  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:]
101110953  CASP9; caspase-9 [KO:K04399] [EC:]
780444  BAD; bcl2-associated agonist of cell death [KO:K02158]
101107877  FOXO1; forkhead box protein O1 [KO:K07201]
100302083  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
101104979  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:]
101103187  E3 ubiquitin-protein ligase Mdm2-like [KO:K06643] [EC:]
443421  TP53; cellular tumor antigen p53 [KO:K04451]
100169938  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:]
443118  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870]
100216465  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
101107485  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X2 [KO:K09048]
101114243  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X2 [KO:K09048]
101108743  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
101113586  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
101113882  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
101112976  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X2 [KO:K09047]
100294600  CTNNB1; catenin beta-1 [KO:K02105]
101110136  EP300; LOW QUALITY PROTEIN: histone acetyltransferase p300 [KO:K04498] [EC:]
101123600  CREBBP; CREB-binding protein [KO:K04498] [EC:]
101101980  TCF7; transcription factor 7 isoform X1 [KO:K02620]
100913162  TCF7L1; transcription factor 7-like 1 [KO:K04490]
101118068  TCF7L2; LOW QUALITY PROTEIN: transcription factor 7-like 2 [KO:K04491]
780521  LEF1; lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
100144763  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
101111143  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:]
780484  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:]
101107332  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
780520  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101108228  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101102191  RELA; transcription factor p65 [KO:K04735]
101119602  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100271659  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:]
101109893  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
114110058  growth factor receptor-bound protein 2 [KO:K04364]
101118865  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
101102732  SOS2; son of sevenless homolog 2 [KO:K03099]
101104357  HRAS; GTPase HRas isoform X1 [KO:K02833]
114114919  GTPase HRas-like [KO:K02833]
101114005  KRAS; GTPase KRas isoform X1 [KO:K07827]
101102438  NRAS; GTPase NRas [KO:K07828]
100305131  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:]
101107438  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:]
101103190  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:]
101123635  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:]
101113846  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:]
101115485  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
101123008  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
100820756  SRD5A2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:]
443042  AR; androgen receptor [KO:K08557]
100127209  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
101117797  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
101111703  HSP90B1; endoplasmin [KO:K09487]
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
Nelson WG, De Marzo AM, Isaacs WB.
Prostate cancer.
N Engl J Med 349:366-81 (2003)
Li L, Ittmann MM, Ayala G, Tsai MJ, Amato RJ, Wheeler TM, Miles BJ, Kadmon D, Thompson TC.
The emerging role of the PI3-K-Akt pathway in prostate cancer progression.
Prostate Cancer Prostatic Dis 8:108-18 (2005)
Pienta KJ, Bradley D.
Mechanisms underlying the development of androgen-independent prostate cancer.
Clin Cancer Res 12:1665-71 (2006)
Feldman BJ, Feldman D.
The development of androgen-independent prostate cancer.
Nat Rev Cancer 1:34-45 (2001)
Heinlein CA, Chang C.
Androgen receptor in prostate cancer.
Endocr Rev 25:276-308 (2004)
Koivisto P, Kolmer M, Visakorpi T, Kallioniemi OP.
Androgen receptor gene and hormonal therapy failure of prostate cancer.
Am J Pathol 152:1-9 (1998)
Zhao XY, Malloy PJ, Krishnan AV, Swami S, Navone NM, Peehl DM, Feldman D.
Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor.
Nat Med 6:703-6 (2000)
Macri E, Loda M.
Role of p27 in prostate carcinogenesis.
Cancer Metastasis Rev 17:337-44 (1998)
Steers WD.
5alpha-reductase activity in the prostate.
Urology 58:17-24; discussion 24 (2001)
Lin D, Meyer DJ, Ketterer B, Lang NP, Kadlubar FF.
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.
Cancer Res 54:4920-6 (1994)
Grimes CA, Jope RS.
The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling.
Prog Neurobiol 65:391-426 (2001)
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
TMPRSS2/ERG promotes epithelial to mesenchymal transition through the ZEB1/ZEB2 axis in a prostate cancer model.
PLoS One 6:e21650 (2011)
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
An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression.
Cancer Cell 17:443-54 (2010)
Squire JA
TMPRSS2-ERG and PTEN loss in prostate cancer.
Nat Genet 41:509-10 (2009)
Adamo P, Ladomery MR
The oncogene ERG: a key factor in prostate cancer.
Oncogene 35:403-14 (2016)
Burdova A, Bouchal J, Tavandzis S, Kolar Z
TMPRSS2-ERG gene fusion in prostate cancer.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 158:502-10 (2014)
Helgeson BE, Tomlins SA, Shah N, Laxman B, Cao Q, Prensner JR, Cao X, Singla N, Montie JE, Varambally S, Mehra R, Chinnaiyan AM
Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 gene fusions in prostate cancer.
Cancer Res 68:73-80 (2008)
Kim H, Datta A, Talwar S, Saleem SN, Mondal D, Abdel-Mageed AB
Estradiol-ERbeta2 signaling axis confers growth and migration of CRPC cells through TMPRSS2-ETV5 gene fusion.
Oncotarget 8:62820-62833 (2017)
oas00140  Steroid hormone biosynthesis
oas04010  MAPK signaling pathway
oas04060  Cytokine-cytokine receptor interaction
oas04110  Cell cycle
oas04115  p53 signaling pathway
oas04151  PI3K-Akt signaling pathway
oas04210  Apoptosis
oas05202  Transcriptional misregulation in cancer
KO pathway

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