KEGG   PATHWAY: pon05215
pon05215                    Pathway                                

Prostate cancer - Pongo abelii (Sumatran orangutan)
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
pon05215  Prostate cancer

Pongo abelii (Sumatran orangutan) [GN:pon]
100174544  GSTP1; glutathione S-transferase P [KO:K23790] [EC:]
100449905  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
100446748  CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:]
100438282  CCNE2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
100461587  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
100462155  RB1; retinoblastoma-associated protein [KO:K06618]
100435851  E2F1; transcription factor E2F1 [KO:K17454]
100458002  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
100448297  E2F3; transcription factor E2F3 isoform X3 [KO:K06620]
100446360  TMPRSS2; transmembrane protease serine 2 isoform X1 [KO:K09633] [EC:3.4.21.-]
100460975  ERG; transcriptional regulator ERG isoform X2 [KO:K09435]
100171578  PLAU; urokinase-type plasminogen activator precursor [KO:K01348] [EC:]
100173068  PLAT; tissue-type plasminogen activator precursor [KO:K01343] [EC:]
100461529  MMP3; stromelysin-1 [KO:K01394] [EC:]
100455867  MMP9; LOW QUALITY PROTEIN: matrix metalloproteinase-9 [KO:K01403] [EC:]
100171534  ZEB1; zinc finger E-box-binding homeobox 1 [KO:K09299]
100440034  IL1R2; interleukin-1 receptor type 2 [KO:K04387]
100436466  SPINT1; kunitz-type protease inhibitor 1 isoform X1 [KO:K15619]
100459983  ETV5; ETS translocation variant 5 isoform X1 [KO:K15593]
100453978  INS; insulin isoform X1 [KO:K04526]
100440212  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
100460243  PDGFB; platelet-derived growth factor subunit B [KO:K17386]
100437861  PDGFC; platelet-derived growth factor C [KO:K05450]
100172718  PDGFD; platelet-derived growth factor D precursor [KO:K05450]
100455021  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
100172994  TGFA; protransforming growth factor alpha precursor [KO:K08774]
100444645  IGF1; insulin-like growth factor I isoform X2 [KO:K05459]
100451898  INSRR; insulin receptor-related protein [KO:K05086] [EC:]
100431735  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:]
100460001  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:]
100174545  FGFR1; fibroblast growth factor receptor 1 precursor [KO:K04362] [EC:]
100171540  FGFR2; fibroblast growth factor receptor 2 [KO:K05093] [EC:]
100459280  EGFR; epidermal growth factor receptor isoform X2 [KO:K04361] [EC:]
100450307  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:]
100172156  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:]
100432846  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:]
100453779  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
103889133  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:]
100174298  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100173589  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
100437617  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100171828  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:]
100452403  LOW QUALITY PROTEIN: 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:]
112129400  LOW QUALITY PROTEIN: putative 3-phosphoinositide-dependent protein kinase 2 [KO:K06276] [EC:]
100436271  NKX3-1; homeobox protein Nkx-3.1 [KO:K09348]
100454279  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
100448114  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:]
100442100  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:]
100460459  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:]
100454097  BAD; bcl2-associated agonist of cell death [KO:K02158]
100460676  FOXO1; forkhead box protein O1 [KO:K07201]
100453682  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
100171532  MDM2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:]
100435218  TP53; cellular tumor antigen p53 [KO:K04451]
100447772  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:]
100294619  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
100462459  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100431578  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
100432292  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
100436186  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
100438869  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
100127093  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
100441756  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100439720  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
100173739  CTNNB1; catenin beta-1 [KO:K02105]
100455260  EP300; histone acetyltransferase p300 isoform X2 [KO:K04498] [EC:]
100445634  CREBBP; LOW QUALITY PROTEIN: CREB-binding protein [KO:K04498] [EC:]
100461234  TCF7; transcription factor 7 isoform X1 [KO:K02620]
100436197  TCF7L1; transcription factor 7-like 1 [KO:K04490]
100434811  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
100447785  LEF1; lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
100171625  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
100174735  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:]
100440586  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X3 [KO:K07209] [EC:]
100449496  IKBKG; NF-kappa-B essential modulator isoform X5 [KO:K07210]
100459445  NF-kappa-B inhibitor alpha [KO:K04734]
100461595  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100456049  RELA; transcription factor p65 [KO:K04735]
100938429  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
100456786  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:]
100173972  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100434331  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
100458733  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100459427  HRAS; GTPase HRas [KO:K02833]
100462513  KRAS; GTPase KRas isoform X1 [KO:K07827]
100174317  NRAS; GTPase NRas precursor [KO:K07828]
100431871  ARAF; serine/threonine-protein kinase A-Raf isoform X4 [KO:K08845] [EC:]
100442288  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:]
100173732  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:]
100446021  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
100450988  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
100169740  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:]
100431824  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:]
100454013  SRD5A2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:]
100171490  AR; androgen receptor [KO:K08557]
100173428  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
100173221  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
100445801  LOW QUALITY PROTEIN: putative heat shock protein HSP 90-alpha A5 [KO:K04079]
100447247  heat shock protein HSP 90-beta-like [KO:K04079]
100174651  HSP90B1; endoplasmin precursor [KO:K09487]
100432364  KLK3; prostate-specific antigen isoform X1 [KO:K01351] [EC:]
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)
pon00140  Steroid hormone biosynthesis
pon04010  MAPK signaling pathway
pon04060  Cytokine-cytokine receptor interaction
pon04110  Cell cycle
pon04115  p53 signaling pathway
pon04151  PI3K-Akt signaling pathway
pon04210  Apoptosis
pon05202  Transcriptional misregulation in cancer
KO pathway

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