KEGG   PATHWAY: pleu05215
Entry
pleu05215                   Pathway                                
Name
Prostate cancer - Peromyscus leucopus (white-footed mouse)
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
pleu05215  Prostate cancer
pleu05215

Disease
H00024  Prostate cancer
Organism
Peromyscus leucopus (white-footed mouse) [GN:pleu]
Gene
114680676  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
114680796  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
114680857  Tgfa; protransforming growth factor alpha isoform X1 [KO:K08774]
114681143  Spint1; kunitz-type protease inhibitor 1 [KO:K15619]
114681270  Ctnnb1; catenin beta-1 isoform X1 [KO:K02105]
114681341  Fgfr1; fibroblast growth factor receptor 1 isoform X4 [KO:K04362] [EC:2.7.10.1]
114681524  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114681591  Tcf7l1; transcription factor 7-like 1 isoform X1 [KO:K04490]
114681621  Sos1; son of sevenless homolog 1 [KO:K03099]
114681779  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
114682099  Rela; transcription factor p65 [KO:K04735]
114682214  Pdgfa; platelet-derived growth factor subunit A [KO:K04359]
114682692  Egf; pro-epidermal growth factor [KO:K04357]
114682732  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
114682737  Grm5; metabotropic glutamate receptor 5 isoform X1 [KO:K04604]
114682738  Folh1b; putative N-acetylated-alpha-linked acidic dipeptidase isoform X1 [KO:K14592] [EC:3.4.17.21]
114682816  Lef1; lymphoid enhancer-binding factor 1 isoform X1 [KO:K04492]
114683055  Tcf7; transcription factor 7 isoform X2 [KO:K02620]
114683205  Nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
114683362  Insrr; LOW QUALITY PROTEIN: insulin receptor-related protein [KO:K05086] [EC:2.7.10.1]
114683759  Pdgfra; platelet-derived growth factor receptor alpha isoform X1 [KO:K04363] [EC:2.7.10.1]
114684032  Pik3cd; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
114684224  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
114685127  [KO:K02833]
114685664  Tmprss2; transmembrane protease serine 2 isoform X1 [KO:K09633] [EC:3.4.21.122]
114686218  [KO:K04079]
114686464  Grm1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
114687991  [KO:K04374]
114688121  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
114688126  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
114688488  [KO:K02833]
114688966  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
114689372  [KO:K09435]
114689636  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
114689726  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
114690660  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
114690861  Il1r2; interleukin-1 receptor type 2 isoform X2 [KO:K04387]
114691010  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
114691497  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
114691504  Slc46a1; proton-coupled folate transporter [KO:K14613]
114691694  [KO:K04079]
114692385  Fgfr2; fibroblast growth factor receptor 2 isoform X2 [KO:K05093] [EC:2.7.10.1]
114692635  Mmp9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
114693171  Tp53; cellular tumor antigen p53 [KO:K04451]
114693314  Mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X1 [KO:K06643] [EC:2.3.2.27]
114693378  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
114693493  [KO:K02833]
114693559  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
114693595  Hras; GTPase HRas isoform X1 [KO:K02833]
114694276  Pdgfb; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
114694285  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
114694299  Ep300; histone acetyltransferase p300 isoform X1 [KO:K04498] [EC:2.3.1.48]
114694498  Ccnd1; G1/S-specific cyclin-D1 isoform X2 [KO:K04503]
114694576  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
114694764  [KO:K23790]
114694770  [KO:K23790]
114695174  Ins; insulin [KO:K04526]
114695335  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
114695462  Igf1r; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
114695568  Zeb1; zinc finger E-box-binding homeobox 1 isoform X1 [KO:K09299]
114695777  [KO:K09487]
114695858  Foxo1; LOW QUALITY PROTEIN: forkhead box protein O1 [KO:K07201]
114696100  Srd5a2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [KO:K12344] [EC:1.3.1.22]
114696521  Slc19a1; reduced folate transporter [KO:K14609]
114696553  [KO:K02833]
114697060  Tcf7l2; transcription factor 7-like 2 isoform X1 [KO:K04491]
114697120  Etv5; ETS translocation variant 5 isoform X1 [KO:K15593]
114697224  E2f2; transcription factor E2F2 isoform X1 [KO:K09389]
114698582  Nras; GTPase NRas [KO:K07828]
114698792  Rb1; retinoblastoma-associated protein isoform X1 [KO:K06618]
114698889  Ccne1; G1/S-specific cyclin-E1 isoform X1 [KO:K06626]
114699702  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
114700209  Plau; urokinase-type plasminogen activator [KO:K01348] [EC:3.4.21.73]
114700362  Erg; transcriptional regulator ERG isoform X1 [KO:K09435]
114700491  Pdgfc; platelet-derived growth factor C isoform X1 [KO:K05450]
114700616  Hsp90b1; endoplasmin [KO:K09487]
114700619  Igf1; insulin-like growth factor I isoform X2 [KO:K05459]
114700859  Casp9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
114701050  E2f3; transcription factor E2F3 isoform X1 [KO:K06620]
114701479  Gsk3b; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
114702670  Nkx3-1; homeobox protein Nkx-3.1 [KO:K09348]
114702810  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
114703046  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
114703084  Hsp90aa1; heat shock protein HSP 90-alpha [KO:K04079]
114703161  Ar; androgen receptor [KO:K08557]
114703207  Creb3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
114703850  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
114703900  Araf; serine/threonine-protein kinase A-Raf isoform X2 [KO:K08845] [EC:2.7.11.1]
114704332  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
114705057  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
114705532  Egfr; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
114705738  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
114705746  Plat; tissue-type plasminogen activator [KO:K01343] [EC:3.4.21.68]
114706157  Cdkn1a; cyclin-dependent kinase inhibitor 1 [KO:K06625]
114706175  Ikbkg; NF-kappa-B essential modulator isoform X1 [KO:K07210]
114706431  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
114706553  E2f1; LOW QUALITY PROTEIN: transcription factor E2F1 [KO:K17454]
114706605  [KO:K13649]
114706689  [KO:K13649]
114706830  Braf; LOW QUALITY PROTEIN: serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
114706924  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
114706940  Erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
114707024  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
114707365  Pdgfrb; LOW QUALITY PROTEIN: platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
114707842  Hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
114707907  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
114708007  Pdgfd; platelet-derived growth factor D isoform X1 [KO:K05450]
114708015  [KO:K01394] [EC:3.4.24.17]
114708477  Kras; GTPase KRas isoform X2 [KO:K07827]
114709670  Mtor; LOW QUALITY PROTEIN: serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
114710338  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
114710523  [KO:K04371] [EC:2.7.11.24]
114710614  [KO:K04498] [EC:2.3.1.48]
Compound
C00025  L-Glutamate
C00280  Androstenedione
C00410  Progesterone
C00504  Folate
C00535  Testosterone
C00735  Cortisol
C00762  Cortisone
C00951  Estradiol-17beta
C01042  N-Acetyl-L-aspartate
C01227  Dehydroepiandrosterone
C03917  Dihydrotestosterone
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C07653  Flutamide
C12270  N-Acetylaspartylglutamate
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
Reference
PMID:38977769
  Authors
Bakht MK, Beltran H
  Title
Biological determinants of PSMA expression, regulation and heterogeneity in prostate cancer.
  Journal
Nat Rev Urol 22:26-45 (2025)
DOI:10.1038/s41585-024-00900-z
Related
pathway
pleu00140  Steroid hormone biosynthesis
pleu04010  MAPK signaling pathway
pleu04060  Cytokine-cytokine receptor interaction
pleu04110  Cell cycle
pleu04115  p53 signaling pathway
pleu04151  PI3K-Akt signaling pathway
pleu04210  Apoptosis
pleu04981  Folate transport and metabolism
pleu05202  Transcriptional misregulation in cancer
KO pathway
ko05215   

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