KEGG   PATHWAY: dord05215
Entry
dord05215                   Pathway                                
Name
Prostate cancer - Dipodomys ordii (Ord's kangaroo rat)
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
dord05215  Prostate cancer
dord05215

Organism
Dipodomys ordii (Ord's kangaroo rat) [GN:dord]
Gene
105989131  glutathione S-transferase P-like [KO:K23790] [EC:2.5.1.18]
105989276  glutathione S-transferase P [KO:K23790] [EC:2.5.1.18]
105992216  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
105990005  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
105993146  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
105982827  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
105980484  Rb1; retinoblastoma-associated protein isoform X1 [KO:K06618]
105981580  E2f1; transcription factor E2F1 [KO:K17454]
105997893  E2f2; transcription factor E2F2 [KO:K09389]
105996367  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
105993941  Tmprss2; transmembrane protease serine 2 isoform X1 [KO:K09633] [EC:3.4.21.122]
105994116  Erg; transcriptional regulator ERG isoform X1 [KO:K09435]
105992685  Plau; urokinase-type plasminogen activator [KO:K01348] [EC:3.4.21.73]
105993280  Plat; tissue-type plasminogen activator isoform X1 [KO:K01343] [EC:3.4.21.68]
105980671  stromelysin-1-like [KO:K01394] [EC:3.4.24.17]
105981538  Mmp9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
105984506  Zeb1; zinc finger E-box-binding homeobox 1 isoform X1 [KO:K09299]
105988217  Il1r2; interleukin-1 receptor type 2 isoform X1 [KO:K04387]
105999710  Etv5; ETS translocation variant 5 [KO:K15593]
105989171  Ins; insulin [KO:K04526]
105990925  Pdgfa; platelet-derived growth factor subunit A isoform X1 [KO:K04359]
105992028  Pdgfb; platelet-derived growth factor subunit B [KO:K17386]
105980590  Pdgfd; platelet-derived growth factor D [KO:K05450]
105995943  Pdgfc; platelet-derived growth factor C [KO:K05450]
105991200  Egf; pro-epidermal growth factor [KO:K04357]
105990143  Tgfa; protransforming growth factor alpha [KO:K08774]
105988510  Igf1; insulin-like growth factor I isoform X1 [KO:K05459]
105996548  Insrr; insulin receptor-related protein [KO:K05086] [EC:2.7.10.1]
105980318  Pdgfra; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
105992616  Pdgfrb; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
105992799  Fgfr1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
105989771  Fgfr2; fibroblast growth factor receptor 2 isoform X1 [KO:K05093] [EC:2.7.10.1]
106000675  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
106003227  Erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
105982453  Igf1r; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
105999080  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105999614  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
106000559  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform-like isoform X1 [KO:K00922] [EC:2.7.1.153]
106001473  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105985370  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105986178  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
105986227  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]
105982143  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
105999400  Nkx3-1; homeobox protein Nkx-3.1 [KO:K09348]
105986533  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105983045  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105998099  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
105989961  Casp9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
105989249  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
105997128  Foxo1; forkhead box protein O1 [KO:K07201]
105995758  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
105990389  Mdm2; E3 ubiquitin-protein ligase Mdm2 [KO:K06643] [EC:2.3.2.27]
105983546  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
105987982  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
105980592  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105992070  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105990397  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
105984920  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
105996036  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
105993372  Creb3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
105989574  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105991729  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
105991983  Ep300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
105981875  Crebbp; CREB-binding protein [KO:K04498] [EC:2.3.1.48]
105996789  Tcf7; transcription factor 7 isoform X1 [KO:K02620]
106000204  Tcf7l1; transcription factor 7-like 1 [KO:K04490]
105986725  Tcf7l2; transcription factor 7-like 2 [KO:K04491]
105991153  Lef1; lymphoid enhancer-binding factor 1 [KO:K04492]
105989065  Ccnd1; G1/S-specific cyclin-D1 [KO:K04503]
105986731  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
105991714  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
106000155  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
105982592  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
105991225  Nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
105989242  Rela; transcription factor p65 isoform X1 [KO:K04735]
105987599  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
105997410  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
106003155  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
105986795  Sos1; son of sevenless homolog 1 [KO:K03099]
105982575  Sos2; son of sevenless homolog 2 [KO:K03099]
105998617  Hras; GTPase HRas isoform X1 [KO:K02833]
105992272  Kras; GTPase KRas isoform X1 [KO:K07827]
105991947  Nras; GTPase NRas [KO:K07828]
106000303  Araf; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
105989470  Braf; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
105981244  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
105981136  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105990471  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
105981830  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105997225  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105983654  Srd5a2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:1.3.1.22]
105997271  Ar; androgen receptor [KO:K08557]
105984907  Hsp90aa1; heat shock protein HSP 90-alpha [KO:K04079]
105987770  Hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
105989225  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
dord00140  Steroid hormone biosynthesis
dord04010  MAPK signaling pathway
dord04060  Cytokine-cytokine receptor interaction
dord04110  Cell cycle
dord04115  p53 signaling pathway
dord04151  PI3K-Akt signaling pathway
dord04210  Apoptosis
dord05202  Transcriptional misregulation in cancer
KO pathway
ko05215   
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