KEGG   PATHWAY: pale05215
Entry
pale05215                   Pathway                                
Name
Prostate cancer - Pteropus alecto (black flying fox)
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
pale05215  Prostate cancer
pale05215

Organism
Pteropus alecto (black flying fox) [GN:pale]
Gene
102889068  glutathione S-transferase P isoform X2 [KO:K23790] [EC:2.5.1.18]
102896271  glutathione S-transferase P [KO:K23790] [EC:2.5.1.18]
102880085  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
102893397  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
102882411  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
102882260  CCNE1; LOW QUALITY PROTEIN: G1/S-specific cyclin-E1 [KO:K06626]
102893019  RB1; retinoblastoma-associated protein [KO:K06618]
102895276  E2F1; transcription factor E2F1 [KO:K17454]
102884459  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
102887239  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102884423  TMPRSS2; transmembrane protease serine 2 [KO:K09633] [EC:3.4.21.122]
102886836  ERG; transcriptional regulator ERG isoform X1 [KO:K09435]
102880095  PLAU; urokinase-type plasminogen activator [KO:K01348] [EC:3.4.21.73]
102893511  PLAT; tissue-type plasminogen activator [KO:K01343] [EC:3.4.21.68]
102886139  stromelysin-1 [KO:K01394] [EC:3.4.24.17]
102889517  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
102879625  ZEB1; zinc finger E-box-binding homeobox 1 [KO:K09299]
102884188  IL1R2; interleukin-1 receptor type 2 [KO:K04387]
102892287  SPINT1; kunitz-type protease inhibitor 1 [KO:K15619]
102882781  ETV5; ETS translocation variant 5 [KO:K15593]
102881117  insulin [KO:K04526]
102893670  PDGFA; platelet-derived growth factor subunit A [KO:K04359]
102897699  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
102894123  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
102890668  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
102891552  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
102887662  TGFA; protransforming growth factor alpha isoform X1 [KO:K08774]
102890331  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
102893617  INSRR; insulin receptor-related protein [KO:K05086] [EC:2.7.10.1]
102895362  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
102887643  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
102898943  FGFR1; fibroblast growth factor receptor 1 isoform X9 [KO:K04362] [EC:2.7.10.1]
102882899  FGFR2; fibroblast growth factor receptor 2 isoform X8 [KO:K05093] [EC:2.7.10.1]
102893495  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
102885300  ERBB2; LOW QUALITY PROTEIN: receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
102885962  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
102889227  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102880320  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102889576  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
102879163  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102891637  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X3 [KO:K02649]
102879453  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102881949  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]
102896950  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
102880253  NKX3-1; homeobox protein Nkx-3.1 [KO:K09348]
102885144  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102879337  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102898305  AKT2; LOW QUALITY PROTEIN: RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102878565  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
102877892  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
102892244  FOXO1; forkhead box protein O1 [KO:K07201]
102894049  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102884281  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
102889604  TP53; cellular tumor antigen p53 [KO:K04451]
102882441  GSK3B; glycogen synthase kinase-3 beta isoform X4 [KO:K03083] [EC:2.7.11.26]
102888198  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
102896553  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102878515  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
102894633  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
102882888  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
102886510  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
102879289  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
102884583  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
102880017  CTNNB1; LOW QUALITY PROTEIN: catenin beta-1 [KO:K02105]
102886172  CREBBP; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:2.3.1.48]
102881042  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
102885788  TCF7; transcription factor 7 isoform X4 [KO:K02620]
102886093  TCF7L1; transcription factor 7-like 1 [KO:K04490]
102880370  TCF7L2; transcription factor 7-like 2 isoform X2 [KO:K04491]
102886933  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
102885330  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102879469  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
102893261  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
102880203  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
102891056  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102880692  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
102878395  RELA; transcription factor p65 [KO:K04735]
102896443  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
102885092  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
102878822  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
102882462  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102889597  SOS2; son of sevenless homolog 2 [KO:K03099]
102896270  HRAS; GTPase HRas isoform X3 [KO:K02833]
102895590  KRAS; GTPase KRas isoform X1 [KO:K07827]
102885950  NRAS; GTPase NRas isoform X2 [KO:K07828]
102877877  ARAF; serine/threonine-protein kinase A-Raf isoform X2 [KO:K08845] [EC:2.7.11.1]
102878393  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
102893439  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102897122  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102879034  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102895390  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102885749  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102884992  SRD5A2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:1.3.1.22]
102893723  LOW QUALITY PROTEIN: androgen receptor-like [KO:K08557]
102894221  AR; androgen receptor [KO:K08557]
102879632  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
102887985  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
102889156  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
pale00140  Steroid hormone biosynthesis
pale04010  MAPK signaling pathway
pale04060  Cytokine-cytokine receptor interaction
pale04110  Cell cycle
pale04115  p53 signaling pathway
pale04151  PI3K-Akt signaling pathway
pale04210  Apoptosis
pale05202  Transcriptional misregulation in cancer
KO pathway
ko05215   
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