KEGG   PATHWAY: shr05215
Entry
shr05215                    Pathway                                
Name
Prostate cancer - Sarcophilus harrisii (Tasmanian devil)
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
shr05215  Prostate cancer
shr05215

Organism
Sarcophilus harrisii (Tasmanian devil) [GN:shr]
Gene
100917755  GSTP1; glutathione S-transferase P [KO:K23790] [EC:2.5.1.18]
100928055  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X1 [KO:K06624]
100925631  CDK2; cyclin-dependent kinase 2 isoform X4 [KO:K02206] [EC:2.7.11.22]
100920942  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
100924454  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
100914196  RB1; retinoblastoma-associated protein [KO:K06618]
116421696  E2F1; transcription factor E2F1 isoform X1 [KO:K17454]
100921594  E2F2; transcription factor E2F2 [KO:K09389]
100934669  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
100918800  TMPRSS2; transmembrane protease serine 2 [KO:K09633] [EC:3.4.21.122]
100926733  ERG; transcriptional regulator ERG isoform X4 [KO:K09435]
100918318  PLAU; urokinase-type plasminogen activator [KO:K01348] [EC:3.4.21.73]
100928675  PLAT; tissue-type plasminogen activator [KO:K01343] [EC:3.4.21.68]
100934169  stromelysin-1 [KO:K01394] [EC:3.4.24.17]
100934566  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
100917269  ZEB1; zinc finger E-box-binding homeobox 1 isoform X3 [KO:K09299]
100913252  IL1R2; interleukin-1 receptor type 2 isoform X1 [KO:K04387]
100933182  SPINT1; kunitz-type protease inhibitor 1 [KO:K15619]
100923882  ETV5; ETS translocation variant 5 isoform X1 [KO:K15593]
100924985  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
116422035  platelet-derived growth factor subunit A-like [KO:K04359]
100917875  PDGFB; platelet-derived growth factor subunit B isoform X2 [KO:K17386]
100928148  PDGFC; platelet-derived growth factor C [KO:K05450]
100916102  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
100933169  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
100928770  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
100918816  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
100926757  INSRR; insulin receptor-related protein [KO:K05086] [EC:2.7.10.1]
100925116  PDGFRA; platelet-derived growth factor receptor alpha isoform X2 [KO:K04363] [EC:2.7.10.1]
100917212  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
100914347  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
100932215  FGFR2; fibroblast growth factor receptor 2 isoform X4 [KO:K05093] [EC:2.7.10.1]
100914017  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
100914727  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
100916673  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
100929811  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100932099  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105749979  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100926892  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100924976  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
100935230  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100927199  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]
100917568  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
100913737  NKX3-1; homeobox protein Nkx-3.1 [KO:K09348]
100917987  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100913262  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100925440  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100931481  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
100923199  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
100928882  FOXO1; forkhead box protein O1 [KO:K07201]
100926666  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100919874  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
100920321  E3 ubiquitin-protein ligase Mdm2-like isoform X1 [KO:K06643] [EC:2.3.2.27]
100922473  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
100920192  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100913327  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100913697  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100926416  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
100913890  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
100916355  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
100917654  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100923082  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
100922067  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
100930636  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
100921187  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
100926283  CREBBP; CREB-binding protein isoform X2 [KO:K04498] [EC:2.3.1.48]
100930141  TCF7; transcription factor 7 isoform X1 [KO:K02620]
100922609  TCF7L1; transcription factor 7-like 1 [KO:K04490]
100922675  TCF7L2; transcription factor 7-like 2 isoform X11 [KO:K04491]
100934638  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
100917462  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100913624  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100928932  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
100926701  IKBKG; NF-kappa-B essential modulator isoform X3 [KO:K07210]
100919027  NFKBIA; LOW QUALITY PROTEIN: NF-kappa-B inhibitor alpha [KO:K04734]
100917619  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100932473  RELA; transcription factor p65 [KO:K04735]
100934666  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100931480  MTOR; serine/threonine-protein kinase mTOR isoform X1 [KO:K07203] [EC:2.7.11.1]
100928380  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100931009  SOS1; son of sevenless homolog 1 isoform X2 [KO:K03099]
100932999  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
100929168  ras-like protein [KO:K02833]
116419913  HRAS; GTPase HRas [KO:K02833]
100915526  KRAS; GTPase KRas isoform X1 [KO:K07827]
100927252  ras-related protein Rab-26-like [KO:K07827]
100929426  ras protein let-60-like [KO:K07827]
100928986  NRAS; GTPase NRas [KO:K07828]
100913901  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
100934801  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
100935202  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
100921899  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
100917396  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
100934330  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100913231  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100934924  SRD5A2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:1.3.1.22]
100933955  AR; androgen receptor [KO:K08557]
100928900  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
100929957  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
100917881  HSP90B1; endoplasmin [KO:K09487]
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
shr00140  Steroid hormone biosynthesis
shr04010  MAPK signaling pathway
shr04060  Cytokine-cytokine receptor interaction
shr04110  Cell cycle
shr04115  p53 signaling pathway
shr04151  PI3K-Akt signaling pathway
shr04210  Apoptosis
shr05202  Transcriptional misregulation in cancer
KO pathway
ko05215   
LinkDB

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