KEGG   PATHWAY: mun05215
Entry
mun05215                    Pathway                                
Name
Prostate cancer - Meriones unguiculatus (Mongolian gerbil)
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
mun05215  Prostate cancer
mun05215

Disease
H00024  Prostate cancer
Organism
Meriones unguiculatus (Mongolian gerbil) [GN:mun]
Gene
110539471  Srd5a2; 3-oxo-5-alpha-steroid 4-dehydrogenase 2 isoform X1 [KO:K12344] [EC:1.3.1.22]
110539539  Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
110539846  Grm5; metabotropic glutamate receptor 5 isoform X1 [KO:K04604]
110540260  Pdgfd; platelet-derived growth factor D isoform X1 [KO:K05450]
110540538  Ar; androgen receptor isoform X1 [KO:K08557]
110541202  Tcf7l1; transcription factor 7-like 1 isoform X1 [KO:K04490]
110541705  Araf; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
110542507  Pdgfc; platelet-derived growth factor C isoform X1 [KO:K05450]
110544642  [KO:K07828]
110544653  [KO:K04467] [EC:2.7.11.10]
110544670  [KO:K13649]
110544765  Nras; GTPase NRas [KO:K07828]
110545060  Casp9; caspase-9 isoform X1 [KO:K04399] [EC:3.4.22.62]
110545091  Slc19a1; reduced folate transporter [KO:K14609]
110545126  Tcf7l2; transcription factor 7-like 2 isoform X10 [KO:K04491]
110545385  E2f2; transcription factor E2F2 [KO:K09389]
110545702  Ccne1; G1/S-specific cyclin-E1 [KO:K06626]
110545779  Braf; serine/threonine-protein kinase B-raf isoform X8 [KO:K04365] [EC:2.7.11.1]
110545943  Crebbp; CREB-binding protein isoform X1 [KO:K04498] [EC:2.3.1.48]
110546586  Cdkn1a; cyclin-dependent kinase inhibitor 1 isoform X2 [KO:K06625]
110546695  Pdgfrb; platelet-derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
110546940  Ccnd1; G1/S-specific cyclin-D1 isoform X2 [KO:K04503]
110547073  Sos1; son of sevenless homolog 1 isoform X1 [KO:K03099]
110547163  Tgfa; protransforming growth factor alpha [KO:K08774]
110547261  Igf1r; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
110547298  Ins; insulin [KO:K04526]
110547825  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
110547978  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
110548120  Etv5; ETS translocation variant 5 [KO:K15593]
110548161  Mtor; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
110548394  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110549145  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
110549233  Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
110549307  Mmp9; matrix metalloproteinase-9 isoform X1 [KO:K01403] [EC:3.4.24.35]
110549347  Rela; transcription factor p65 isoform X1 [KO:K04735]
110549421  Foxo1; forkhead box protein O1 [KO:K07201]
110549622  Tcf7; transcription factor 7 isoform X6 [KO:K02620]
110549859  Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
110550158  Slc46a1; proton-coupled folate transporter [KO:K14613]
110550615  Spint1; kunitz-type protease inhibitor 1 [KO:K15619]
110550699  Pdgfa; platelet-derived growth factor subunit A isoform X3 [KO:K04359]
110550814  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
110551008  Cdkn1b; cyclin-dependent kinase inhibitor 1B [KO:K06624]
110551437  Creb1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
110551603  Bad; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
110552013  Plau; urokinase-type plasminogen activator [KO:K01348] [EC:3.4.21.73]
110552966  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
110553013  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
110553196  Egf; pro-epidermal growth factor [KO:K04357]
110553235  Hsp90aa1; heat shock protein HSP 90-alpha [KO:K04079]
110553391  Lef1; lymphoid enhancer-binding factor 1 isoform X2 [KO:K04492]
110553592  Rb1; retinoblastoma-associated protein [KO:K06618]
110553683  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
110553796  Mapk1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
110553931  Hras; GTPase HRas isoform X1 [KO:K02833]
110554089  Ep300; histone acetyltransferase p300 [KO:K04498] [EC:2.3.1.48]
110554250  Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
110554547  E2f1; transcription factor E2F1 isoform X1 [KO:K17454]
110554945  Nkx3-1; homeobox protein Nkx-3.1 [KO:K09348]
110554946  Fgfr2; fibroblast growth factor receptor 2 isoform X3 [KO:K05093] [EC:2.7.10.1]
110554970  Creb5; cyclic AMP-responsive element-binding protein 5 isoform X2 [KO:K09047]
110555127  Tp53; cellular tumor antigen p53 isoform X1 [KO:K04451]
110555390  Gsk3b; glycogen synthase kinase-3 beta isoform X4 [KO:K03083] [EC:2.7.11.26]
110555605  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
110555614  Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
110555839  Hsp90ab1; heat shock protein HSP 90-beta [KO:K04079]
110556252  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
110556613  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
110556621  Plat; tissue-type plasminogen activator isoform X1 [KO:K01343] [EC:3.4.21.68]
110556719  Akt2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110556913  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
110557555  [KO:K13649]
110557800  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
110557819  Pdgfb; platelet-derived growth factor subunit B isoform X1 [KO:K17386]
110558090  [KO:K01394] [EC:3.4.24.17]
110558105  Pdgfra; platelet-derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
110558602  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X2 [KO:K02580]
110558766  Zeb1; zinc finger E-box-binding homeobox 1 isoform X1 [KO:K09299]
110558913  Kras; GTPase KRas isoform X1 [KO:K07827]
110558966  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
110559000  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
110559398  Cdk2; cyclin-dependent kinase 2 isoform X1 [KO:K02206] [EC:2.7.11.22]
110560369  [KO:K23790]
110560370  [KO:K23790]
110560579  Erg; transcriptional regulator ERG isoform X4 [KO:K09435]
110561175  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]
110561277  Ccne2; G1/S-specific cyclin-E2 isoform X1 [KO:K06626]
110561622  Igf1; insulin-like growth factor I isoform X5 [KO:K05459]
110561755  Ctnnb1; catenin beta-1 [KO:K02105]
110561800  E2f3; transcription factor E2F3 isoform X3 [KO:K06620]
110561822  Il1r2; interleukin-1 receptor type 2 isoform X1 [KO:K04387]
110561882  Creb3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
110562241  Mdm2; E3 ubiquitin-protein ligase Mdm2 isoform X2 [KO:K06643] [EC:2.3.2.27]
110562303  Folh1; glutamate carboxypeptidase 2 [KO:K14592] [EC:3.4.17.21]
110562401  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
110562528  Ikbkg; NF-kappa-B essential modulator isoform X3 [KO:K07210]
110562952  Erbb2; receptor tyrosine-protein kinase erbB-2 [KO:K05083] [EC:2.7.10.1]
110563307  Fgfr1; fibroblast growth factor receptor 1 isoform X1 [KO:K04362] [EC:2.7.10.1]
110563512  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
110563683  Tmprss2; transmembrane protease serine 2 isoform X1 [KO:K09633] [EC:3.4.21.122]
110563924  Hsp90b1; endoplasmin [KO:K09487]
110564629  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
110564898  Akt3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
110564976  Insrr; insulin receptor-related protein isoform X1 [KO:K05086] [EC:2.7.10.1]
110565112  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
110566206  Grm1; metabotropic glutamate receptor 1 isoform X1 [KO:K04603]
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
  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
Reference
  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
mun00140  Steroid hormone biosynthesis
mun04010  MAPK signaling pathway
mun04060  Cytokine-cytokine receptor interaction
mun04110  Cell cycle
mun04115  p53 signaling pathway
mun04151  PI3K-Akt signaling pathway
mun04210  Apoptosis
mun04981  Folate transport and metabolism
mun05202  Transcriptional misregulation in cancer
KO pathway
ko05215   

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