KEGG   PATHWAY: gas05215
Entry
gas05215                    Pathway                                
Name
Prostate cancer - Gracilinanus agilis (agile gracile opossum)
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
gas05215  Prostate cancer
gas05215

Organism
Gracilinanus agilis (agile gracile opossum) [GN:gas]
Gene
123255467  GSTP1; glutathione S-transferase P [KO:K23790] [EC:2.5.1.18]
123248489  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
123248961  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
123235321  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
123251985  G1/S-specific cyclin-E2-like [KO:K06626]
123246605  G1/S-specific cyclin-E2-like [KO:K06626]
123240740  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
123240551  RB1; retinoblastoma-associated protein [KO:K06618]
123235468  E2F1; transcription factor E2F1 [KO:K17454]
123240067  E2F3; transcription factor E2F3 [KO:K06620]
123242510  TMPRSS2; transmembrane protease serine 2 [KO:K09633] [EC:3.4.21.122]
123242496  ERG; transcriptional regulator ERG isoform X1 [KO:K09435]
123236414  PLAU; urokinase-type plasminogen activator isoform X1 [KO:K01348] [EC:3.4.21.73]
123236981  PLAT; tissue-type plasminogen activator [KO:K01343] [EC:3.4.21.68]
123238995  stromelysin-1-like [KO:K01394] [EC:3.4.24.17]
123235271  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
123250734  ZEB1; zinc finger E-box-binding homeobox 1 isoform X1 [KO:K09299]
123241762  IL1R2; interleukin-1 receptor type 2 [KO:K04387]
123235961  SPINT1; LOW QUALITY PROTEIN: kunitz-type protease inhibitor 1 [KO:K15619]
123247559  ETV5; ETS translocation variant 5 [KO:K15593]
123256044  INS; insulin [KO:K04526]
123234190  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
123250075  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
123241052  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
123252942  PDGFC; platelet-derived growth factor C [KO:K05450]
123253141  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
123250427  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
123246087  INSRR; insulin receptor-related protein [KO:K05086] [EC:2.7.10.1]
123252399  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
123233823  PDGFRB; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
123236988  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
123234272  FGFR2; fibroblast growth factor receptor 2 [KO:K05093] [EC:2.7.10.1]
123247456  EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
123245551  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
123238083  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
123242322  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
123242831  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
123240288  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
123236876  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
123256513  phosphatidylinositol 3-kinase regulatory subunit beta-like [KO:K02649]
123256515  phosphatidylinositol 3-kinase regulatory subunit beta-like [KO:K02649]
123233053  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]
123231496  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
123244679  3-phosphoinositide-dependent protein kinase 1-like [KO:K06276] [EC:2.7.11.1]
123234482  NKX3-1; homeobox protein Nkx-3.1 [KO:K09348]
123247425  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123242998  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
123237620  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
123240973  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
123251373  BAD; bcl2-associated agonist of cell death [KO:K02158]
123241253  FOXO1; forkhead box protein O1 [KO:K07201]
123243800  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
123248749  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
123251829  LOW QUALITY PROTEIN: E3 ubiquitin-protein ligase Mdm2-like [KO:K06643] [EC:2.3.2.27]
123244534  TP53; cellular tumor antigen p53 [KO:K04451]
123242376  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
123242713  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
123250763  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
123247071  CREB3L4; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
123242984  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
123249476  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
123232395  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
123252575  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
123250437  CTNNB1; catenin beta-1 [KO:K02105]
123231726  CREB-binding protein [KO:K04498] [EC:2.3.1.48]
123250301  EP300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
123237636  TCF7; transcription factor 7 [KO:K02620]
123233138  TCF7L1; transcription factor 7-like 1 [KO:K04490]
123238173  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
123236476  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
123233417  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
123253779  IKBKG; NF-kappa-B essential modulator [KO:K07210]
123235754  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
123252239  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
123251290  RELA; transcription factor p65 isoform X1 [KO:K04735]
123238254  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
123240305  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
123245523  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
123236829  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
123233974  SOS2; son of sevenless homolog 2 [KO:K03099]
123248684  KRAS; GTPase KRas isoform X1 [KO:K07827]
123251828  LOW QUALITY PROTEIN: GTPase NRas-like [KO:K07827]
123247194  NRAS; GTPase NRas [KO:K07828]
123232515  GTPase NRas-like [KO:K07828]
123253593  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
123249501  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
123239466  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
123238040  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
123243007  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
123230857  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123245714  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
123234969  SRD5A2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:1.3.1.22]
123249349  heat shock protein HSP 90-alpha isoform X1 [KO:K04079]
123245724  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
123248587  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
gas00140  Steroid hormone biosynthesis
gas04010  MAPK signaling pathway
gas04060  Cytokine-cytokine receptor interaction
gas04110  Cell cycle
gas04115  p53 signaling pathway
gas04151  PI3K-Akt signaling pathway
gas04210  Apoptosis
gas05202  Transcriptional misregulation in cancer
KO pathway
ko05215   
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