KEGG   PATHWAY: llv05215
Entry
llv05215                    Pathway                                
Name
Prostate cancer - Lutra lutra (Eurasian river otter)
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
llv05215  Prostate cancer
llv05215

Organism
Lutra lutra (Eurasian river otter) [GN:llv]
Gene
125110256  glutathione S-transferase P-like isoform X1 [KO:K23790] [EC:2.5.1.18]
125110257  glutathione S-transferase P [KO:K23790] [EC:2.5.1.18]
125106593  cyclin-dependent kinase inhibitor 1B [KO:K06624]
125106521  LOW QUALITY PROTEIN: cyclin-dependent kinase 2-like [KO:K02206] [EC:2.7.11.22]
125096979  G1/S-specific cyclin-E2 [KO:K06626]
125089714  G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
125096420  retinoblastoma-associated protein [KO:K06618]
125109172  transcription factor E2F1 isoform X1 [KO:K17454]
125097872  transcription factor E2F2 isoform X1 [KO:K09389]
125102168  transcription factor E2F3 isoform X1 [KO:K06620]
125094004  transmembrane protease serine 2-like [KO:K09633] [EC:3.4.21.122]
125094243  transcriptional regulator ERG isoform X1 [KO:K09435]
125084356  urokinase-type plasminogen activator-like [KO:K01348] [EC:3.4.21.73]
125092797  tissue-type plasminogen activator-like [KO:K01343] [EC:3.4.21.68]
125078732  stromelysin-1 [KO:K01394] [EC:3.4.24.17]
125078733  stromelysin-2-like [KO:K01394] [EC:3.4.24.17]
125109962  matrix metalloproteinase-9 isoform X1 [KO:K01403] [EC:3.4.24.35]
125108004  zinc finger E-box-binding homeobox 1 isoform X1 [KO:K09299]
125109725  interleukin-1 receptor type 2-like isoform X1 [KO:K04387]
125105284  kunitz-type protease inhibitor 1-like [KO:K15619]
125101811  ETS translocation variant 5 [KO:K15593]
125079072  insulin [KO:K04526]
125090848  platelet-derived growth factor subunit A isoform X1 [KO:K04359]
125107099  platelet-derived growth factor subunit B isoform X1 [KO:K17386]
125093106  platelet-derived growth factor C isoform X1 [KO:K05450]
125079346  platelet-derived growth factor D isoform X1 [KO:K05450]
125093282  pro-epidermal growth factor isoform X1 [KO:K04357]
125106739  insulin-like growth factor I isoform X1 [KO:K05459]
125085736  insulin receptor-related protein isoform X1 [KO:K05086] [EC:2.7.10.1]
125093724  platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
125100170  platelet-derived growth factor receptor beta isoform X1 [KO:K05089] [EC:2.7.10.1]
125092758  fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
125084713  fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
125080419  epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
125087205  receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
125105350  insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
125100627  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
125103868  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
125096824  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
125099801  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
125082268  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
125097558  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
125084450  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]
125090410  3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
125092878  homeobox protein Nkx-3.1-like [KO:K09348]
125086439  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125104283  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
125089561  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
125098709  caspase-9-like isoform X1 [KO:K04399] [EC:3.4.22.62]
125079150  bcl2-associated agonist of cell death-like isoform X1 [KO:K02158]
125096352  forkhead box protein O1 isoform X1 [KO:K07201]
125102743  cyclin-dependent kinase inhibitor 1 [KO:K06625]
125107551  E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
125087037  cellular tumor antigen p53 isoform X1 [KO:K04451]
125097853  glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
125095039  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
125106338  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
125083953  cyclic AMP-responsive element-binding protein 3-like [KO:K09048]
125085653  cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
125086626  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
125079521  cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
125080714  cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
125080867  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
125106092  catenin beta-1 [KO:K02105]
125091150  CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
125106189  histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
125099902  transcription factor 7 isoform X1 [KO:K02620]
125108462  transcription factor 7-like 1 isoform X1 [KO:K04490]
125084325  transcription factor 7-like 2 isoform X1 [KO:K04491]
125093264  lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
125078419  G1/S-specific cyclin-D1 [KO:K04503]
125084339  LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit alpha-like [KO:K04467] [EC:2.7.11.10]
125094028  inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
125091312  NF-kappa-B essential modulator isoform X1 [KO:K07210]
125105211  NF-kappa-B inhibitor alpha [KO:K04734]
125093224  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
125078405  transcription factor p65 isoform X1 [KO:K04735]
125081686  apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
125097001  serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
125087106  growth factor receptor-bound protein 2 [KO:K04364]
125109653  LOW QUALITY PROTEIN: son of sevenless homolog 1-like [KO:K03099]
125104149  son of sevenless homolog 2 isoform X1 [KO:K03099]
125078621  GTPase HRas isoform X1 [KO:K02833]
125106241  GTPase KRas isoform X1 [KO:K07827]
125098043  GTPase NRas [KO:K07828]
125091395  serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
125080584  serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
125108469  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
125105594  dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
125086704  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
125081690  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
125090203  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
125109219  3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:1.3.1.22]
125092011  heat shock protein HSP 90-alpha-like [KO:K04079]
125101710  heat shock protein HSP 90-beta [KO:K04079]
125104755  heat shock protein HSP 90-alpha [KO:K04079]
125098939  heat shock protein HSP 90-alpha-like [KO:K04079]
125107935  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
llv00140  Steroid hormone biosynthesis
llv04010  MAPK signaling pathway
llv04060  Cytokine-cytokine receptor interaction
llv04110  Cell cycle
llv04115  p53 signaling pathway
llv04151  PI3K-Akt signaling pathway
llv04210  Apoptosis
llv05202  Transcriptional misregulation in cancer
KO pathway
ko05215   
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