KEGG   PATHWAY: mcf05215
Entry
mcf05215                    Pathway                                
Name
Prostate cancer - Macaca fascicularis (crab-eating macaque)
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
mcf05215  Prostate cancer
mcf05215

Disease
H00024  Prostate cancer
Organism
Macaca fascicularis (crab-eating macaque) [GN:mcf]
Gene
101865178  ETV5; ETS translocation variant 5 [KO:K15593]
101866246  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
101866379  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
101866436  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
101866865  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
101867036  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]
101867139  ZEB1; zinc finger E-box-binding homeobox 1 isoform X1 [KO:K09299]
101867161  PDGFRB; platelet-derived growth factor receptor beta isoform X2 [KO:K05089] [EC:2.7.10.1]
101867324  RELA; transcription factor p65 isoform X1 [KO:K04735]
101867458  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
101925249  ARAF; serine/threonine-protein kinase A-Raf isoform X2 [KO:K08845] [EC:2.7.11.1]
101925349  LEF1; lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
101925936  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
101926380  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
101926487  HSP90B1; endoplasmin [KO:K09487]
102115368  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
102115639  SRD5A2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 isoform X1 [KO:K12344] [EC:1.3.1.22]
102115964  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
102116470  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
102116712  FOXO1; forkhead box protein O1 [KO:K07201]
102116996  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
102117693  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
102117720  AR; androgen receptor isoform X1 [KO:K08557]
102117938  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102117954  CDKN1B; cyclin-dependent kinase inhibitor 1B isoform X2 [KO:K06624]
102118276  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
102118744  HRAS; GTPase HRas [KO:K02833]
102121921  BAD; bcl2-associated agonist of cell death [KO:K02158]
102122045  SPINT1; kunitz-type protease inhibitor 1 isoform X1 [KO:K15619]
102122725  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102122741  ERG; transcriptional regulator ERG isoform X5 [KO:K09435]
102123367  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
102123415  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
102123807  [KO:K04079]
102124804  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102125183  PDGFB; platelet-derived growth factor subunit B isoform X2 [KO:K17386]
102125312  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
102125513  TCF7L1; transcription factor 7-like 1 isoform X1 [KO:K04490]
102126620  PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
102126830  CASP9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
102127415  GSTP1; glutathione S-transferase P isoform X2 [KO:K23790]
102128018  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
102128093  E2F2; transcription factor E2F2 isoform X1 [KO:K09389]
102128214  INSRR; insulin receptor-related protein isoform X2 [KO:K05086] [EC:2.7.10.1]
102128371  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
102130142  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
102131483  KRAS; GTPase KRas isoform X1 [KO:K07827]
102131731  EP300; histone acetyltransferase p300 isoform X2 [KO:K04498] [EC:2.3.1.48]
102132043  PDGFC; platelet-derived growth factor C [KO:K05450]
102132744  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102133184  INS; insulin [KO:K04526]
102133756  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
102134095  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X2 [KO:K09048]
102135037  CREBBP; CREB-binding protein isoform X2 [KO:K04498] [EC:2.3.1.48]
102135079  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102135329  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
102135886  PLAU; urokinase-type plasminogen activator isoform X1 [KO:K01348] [EC:3.4.21.73]
102135998  TP53; cellular tumor antigen P53 [KO:K04451]
102136063  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
102136323  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
102136437  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
102137291  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
102137447  TMPRSS2; transmembrane protease serine 2 isoform X1 [KO:K09633] [EC:3.4.21.122]
102137714  CCNE1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
102137913  NRAS; GTPase NRas [KO:K07828]
102138138  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
102138212  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
102138273  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X3 [KO:K02580]
102138313  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
102138392  PDGFRA; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
102138564  CCNE2; G1/S-specific cyclin-E2 isoform X3 [KO:K06626]
102138599  KLK3; prostate-specific antigen [KO:K01351] [EC:3.4.21.77]
102138724  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
102139233  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
102139679  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
102140855  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
102141214  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
102142026  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102142248  TCF7; LOW QUALITY PROTEIN: transcription factor 7 [KO:K02620]
102142281  NKX3-1; homeobox protein Nkx-3.1 [KO:K09348]
102142378  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
102142406  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102142651  MMP3; stromelysin-1 [KO:K01394] [EC:3.4.24.17]
102143086  FGFR2; fibroblast growth factor receptor 2 isoform X3 [KO:K05093] [EC:2.7.10.1]
102143464  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102143926  IL1R2; interleukin-1 receptor type 2 isoform X2 [KO:K04387]
102144461  AKT3; RAC-gamma serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
102144714  FGFR1; fibroblast growth factor receptor 1 isoform X6 [KO:K04362] [EC:2.7.10.1]
102145011  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102145462  PLAT; tissue-type plasminogen activator [KO:K01343] [EC:3.4.21.68]
102145541  TGFA; protransforming growth factor alpha isoform X2 [KO:K08774]
102145859  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
102146018  E2F1; transcription factor E2F1 [KO:K17454]
102146405  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
102146604  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
102146608  ERBB2; receptor tyrosine-protein kinase ErbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
102146984  CTNNB1; catenin beta-1 isoform X1 [KO:K02105]
135964355  [KO:K07210]
135965514  [KO:K15619]
135965565  [KO:K15619]
135971892  [KO:K23790]
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
mcf00140  Steroid hormone biosynthesis
mcf04010  MAPK signaling pathway
mcf04060  Cytokine-cytokine receptor interaction
mcf04110  Cell cycle
mcf04115  p53 signaling pathway
mcf04151  PI3K-Akt signaling pathway
mcf04210  Apoptosis
mcf05202  Transcriptional misregulation in cancer
KO pathway
ko05215   

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