KEGG   PATHWAY: npo05215
Entry
npo05215                    Pathway                                
Name
Prostate cancer - Nyctereutes procyonoides (raccoon dog)
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
npo05215  Prostate cancer
npo05215

Organism
Nyctereutes procyonoides (raccoon dog) [GN:npo]
Gene
129507966  glutathione S-transferase P-like [KO:K23790] [EC:2.5.1.18]
129503208  glutathione S-transferase P [KO:K23790] [EC:2.5.1.18]
129503209  glutathione S-transferase P-like [KO:K23790] [EC:2.5.1.18]
129520093  glutathione S-transferase P-like [KO:K23790] [EC:2.5.1.18]
129521167  glutathione S-transferase P-like [KO:K23790] [EC:2.5.1.18]
129517176  CDKN1B; cyclin-dependent kinase inhibitor 1B [KO:K06624]
129511299  CDK2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
129501012  CCNE1; G1/S-specific cyclin-E1 [KO:K06626]
129495669  CCNE2; G1/S-specific cyclin-E2 [KO:K06626]
129497562  G1/S-specific cyclin-E1-like [KO:K06626]
129516428  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
129496621  E2F1; transcription factor E2F1 [KO:K17454]
129514246  E2F2; transcription factor E2F2 [KO:K09389]
129507839  E2F3; transcription factor E2F3 isoform X1 [KO:K06620]
129502198  TMPRSS2; transmembrane protease serine 2 isoform X1 [KO:K09633] [EC:3.4.21.122]
129502148  ERG; transcriptional regulator ERG isoform X1 [KO:K09435]
129509321  PLAU; urokinase-type plasminogen activator [KO:K01348] [EC:3.4.21.73]
129516213  PLAT; tissue-type plasminogen activator [KO:K01343] [EC:3.4.21.68]
129497419  stromelysin-1 [KO:K01394] [EC:3.4.24.17]
129496726  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
129515591  ZEB1; zinc finger E-box-binding homeobox 1 isoform X1 [KO:K09299]
129511797  IL1R2; interleukin-1 receptor type 2 isoform X1 [KO:K04387]
129504189  SPINT1; kunitz-type protease inhibitor 1 [KO:K15619]
129498832  ETV5; ETS translocation variant 5 [KO:K15593]
129503213  INS; insulin [KO:K04526]
129519919  PDGFA; platelet-derived growth factor subunit A [KO:K04359]
129512083  PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
129497471  PDGFD; platelet-derived growth factor D isoform X1 [KO:K05450]
129516878  PDGFC; platelet-derived growth factor C isoform X1 [KO:K05450]
129521218  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
129511504  TGFA; protransforming growth factor alpha [KO:K08774]
129516962  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
129508574  INSRR; insulin receptor-related protein isoform X1 [KO:K05086] [EC:2.7.10.1]
129520020  PDGFRA; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
129509546  PDGFRB; platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
129515655  FGFR1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
129523284  FGFR2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
129494118  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
129505762  ERBB2; receptor tyrosine-protein kinase erbB-2 isoform X1 [KO:K05083] [EC:2.7.10.1]
129510268  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
129496789  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
129498637  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
129507069  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
129513452  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
129520803  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
129522073  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
129507556  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]
129519211  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
129493819  NKX3-1; homeobox protein Nkx-3.1 [KO:K09348]
129508823  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129495892  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
129499851  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
129517633  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
129514778  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
129513406  CASP9; caspase-9 [KO:K04399] [EC:3.4.22.62]
129503119  BAD; bcl2-associated agonist of cell death [KO:K02158]
129504466  FOXO1; forkhead box protein O1 [KO:K07201]
129512989  CDKN1A; cyclin-dependent kinase inhibitor 1 [KO:K06625]
129511628  MDM2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
129497070  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
129503652  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
129522997  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
129518269  cyclic AMP-responsive element-binding protein 1-like [KO:K05870]
129511576  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
129508719  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
129494799  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
129503105  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
129515926  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
129522278  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
129502771  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
129506984  CTNNB1; catenin beta-1 [KO:K02105]
129511409  EP300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
129520280  CREBBP; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
129494859  TCF7; transcription factor 7 isoform X1 [KO:K02620]
129510910  TCF7L1; transcription factor 7-like 1 [KO:K04490]
129493862  TCF7L2; transcription factor 7-like 2 isoform X1 [KO:K04491]
129521205  LEF1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
129502968  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
129493669  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
129515857  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
129517602  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
129499457  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
129521190  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
129503049  RELA; transcription factor p65 isoform X1 [KO:K04735]
129495480  apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129514527  apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
129513263  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
129511906  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
129496132  SOS2; son of sevenless homolog 2 [KO:K03099]
129510881  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
129494224  HRAS; GTPase HRas isoform X1 [KO:K02833]
129505561  KRAS; GTPase KRas isoform X1 [KO:K07827]
129501466  NRAS; GTPase NRas [KO:K07828]
129518309  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
129515848  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
129522592  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
129506345  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
129522322  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
129502349  mitogen-activated protein kinase 3-like [KO:K04371] [EC:2.7.11.24]
129507918  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
129519082  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
129511023  SRD5A2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:1.3.1.22]
129517777  AR; androgen receptor [KO:K08557]
129494639  LOW QUALITY PROTEIN: heat shock protein HSP 90-beta-like [KO:K04079]
129496348  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
129513069  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
129516837  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
npo00140  Steroid hormone biosynthesis
npo04010  MAPK signaling pathway
npo04060  Cytokine-cytokine receptor interaction
npo04110  Cell cycle
npo04115  p53 signaling pathway
npo04151  PI3K-Akt signaling pathway
npo04210  Apoptosis
npo05202  Transcriptional misregulation in cancer
KO pathway
ko05215   
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