KEGG   PATHWAY: ko05215
ko05215                     Pathway                                
Prostate cancer
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.
Human Diseases; Cancer: specific types
Pathway map
ko05215  Prostate cancer

H00024  Prostate cancer
K23790  glutathione S-transferase P [EC:]
K06624  cyclin-dependent kinase inhibitor 1B
K02206  cyclin-dependent kinase 2 [EC:]
K06626  G1/S-specific cyclin-E1
K06618  retinoblastoma-associated protein
K17454  transcription factor E2F1
K09389  transcription factor E2F2
K06620  transcription factor E2F3
K09633  transmembrane protease serine 2 [EC:]
K09435  transcriptional regulator ERG
K01348  urokinase plasminogen activator [EC:]
K01343  tissue plasminogen activator [EC:]
K01394  matrix metalloproteinase-3 (stromelysin 1, progelatinase) [EC:]
K01403  matrix metalloproteinase-9 (gelatinase B) [EC:]
K09299  zinc finger homeobox protein 1
K04387  interleukin 1 receptor type II
K15619  Kunitz-type protease inhibitor 1
K15593  ets translocation variant 5
K04526  insulin
K04359  platelet-derived growth factor subunit A
K17386  platelet-derived growth factor subunit B
K05450  platelet derived growth factor C/D
K04357  epidermal growth factor
K08774  transforming growth factor, alpha
K05459  insulin-like growth factor 1
K05086  insulin receptor-related receptor [EC:]
K04363  platelet-derived growth factor receptor alpha [EC:]
K05089  platelet-derived growth factor receptor beta [EC:]
K04362  fibroblast growth factor receptor 1 [EC:]
K05093  fibroblast growth factor receptor 2 [EC:]
K04361  epidermal growth factor receptor [EC:]
K05083  receptor tyrosine-protein kinase erbB-2 [EC:]
K05087  insulin-like growth factor 1 receptor [EC:]
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K01110  phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:]
K06276  3-phosphoinositide dependent protein kinase-1 [EC:]
K09348  homeobox protein Nkx-3.1
K04456  RAC serine/threonine-protein kinase [EC:]
K04399  caspase 9 [EC:]
K02158  Bcl-2-antagonist of cell death
K07201  forkhead box protein O1
K06625  cyclin-dependent kinase inhibitor 1A
K06643  E3 ubiquitin-protein ligase Mdm2 [EC:]
K04451  tumor protein p53
K03083  glycogen synthase kinase 3 beta [EC:]
K05870  cyclic AMP-responsive element-binding protein 1
K04374  cyclic AMP-dependent transcription factor ATF-4
K09048  cyclic AMP-responsive element-binding protein 3
K09047  cyclic AMP-responsive element-binding protein 5
K02105  catenin beta 1
K04498  E1A/CREB-binding protein [EC:]
K02620  transcription factor 7
K04490  transcription factor 7-like 1
K04491  transcription factor 7-like 2
K04492  lymphoid enhancer-binding factor 1
K04503  G1/S-specific cyclin-D1
K04467  inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:]
K07209  inhibitor of nuclear factor kappa-B kinase subunit beta [EC:]
K07210  inhibitor of nuclear factor kappa-B kinase subunit gamma
K04734  NF-kappa-B inhibitor alpha
K02580  nuclear factor NF-kappa-B p105 subunit
K04735  transcription factor p65
K02161  apoptosis regulator Bcl-2
K07203  serine/threonine-protein kinase mTOR [EC:]
K04364  growth factor receptor-bound protein 2
K03099  son of sevenless
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K08845  A-Raf proto-oncogene serine/threonine-protein kinase [EC:]
K04365  B-Raf proto-oncogene serine/threonine-protein kinase [EC:]
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:]
K04368  mitogen-activated protein kinase kinase 1 [EC:]
K04369  mitogen-activated protein kinase kinase 2 [EC:]
K04371  mitogen-activated protein kinase 1/3 [EC:]
K12344  3-oxo-5-alpha-steroid 4-dehydrogenase 2 [EC:]
K08557  androgen receptor
K04079  molecular chaperone HtpG
K09487  heat shock protein 90kDa beta
K01351  semenogelase [EC:]
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
Nelson WG, De Marzo AM, Isaacs WB.
Prostate cancer.
N Engl J Med 349:366-81 (2003)
Li L, Ittmann MM, Ayala G, Tsai MJ, Amato RJ, Wheeler TM, Miles BJ, Kadmon D, Thompson TC.
The emerging role of the PI3-K-Akt pathway in prostate cancer progression.
Prostate Cancer Prostatic Dis 8:108-18 (2005)
Pienta KJ, Bradley D.
Mechanisms underlying the development of androgen-independent prostate cancer.
Clin Cancer Res 12:1665-71 (2006)
Feldman BJ, Feldman D.
The development of androgen-independent prostate cancer.
Nat Rev Cancer 1:34-45 (2001)
Heinlein CA, Chang C.
Androgen receptor in prostate cancer.
Endocr Rev 25:276-308 (2004)
Koivisto P, Kolmer M, Visakorpi T, Kallioniemi OP.
Androgen receptor gene and hormonal therapy failure of prostate cancer.
Am J Pathol 152:1-9 (1998)
Zhao XY, Malloy PJ, Krishnan AV, Swami S, Navone NM, Peehl DM, Feldman D.
Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor.
Nat Med 6:703-6 (2000)
Macri E, Loda M.
Role of p27 in prostate carcinogenesis.
Cancer Metastasis Rev 17:337-44 (1998)
Steers WD.
5alpha-reductase activity in the prostate.
Urology 58:17-24; discussion 24 (2001)
Lin D, Meyer DJ, Ketterer B, Lang NP, Kadlubar FF.
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.
Cancer Res 54:4920-6 (1994)
Grimes CA, Jope RS.
The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling.
Prog Neurobiol 65:391-426 (2001)
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
TMPRSS2/ERG promotes epithelial to mesenchymal transition through the ZEB1/ZEB2 axis in a prostate cancer model.
PLoS One 6:e21650 (2011)
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
An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression.
Cancer Cell 17:443-54 (2010)
Squire JA
TMPRSS2-ERG and PTEN loss in prostate cancer.
Nat Genet 41:509-10 (2009)
Adamo P, Ladomery MR
The oncogene ERG: a key factor in prostate cancer.
Oncogene 35:403-14 (2016)
Burdova A, Bouchal J, Tavandzis S, Kolar Z
TMPRSS2-ERG gene fusion in prostate cancer.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 158:502-10 (2014)
Helgeson BE, Tomlins SA, Shah N, Laxman B, Cao Q, Prensner JR, Cao X, Singla N, Montie JE, Varambally S, Mehra R, Chinnaiyan AM
Characterization of TMPRSS2:ETV5 and SLC45A3:ETV5 gene fusions in prostate cancer.
Cancer Res 68:73-80 (2008)
Kim H, Datta A, Talwar S, Saleem SN, Mondal D, Abdel-Mageed AB
Estradiol-ERbeta2 signaling axis confers growth and migration of CRPC cells through TMPRSS2-ETV5 gene fusion.
Oncotarget 8:62820-62833 (2017)
ko00140  Steroid hormone biosynthesis
ko04010  MAPK signaling pathway
ko04060  Cytokine-cytokine receptor interaction
ko04110  Cell cycle
ko04115  p53 signaling pathway
ko04151  PI3K-Akt signaling pathway
ko04210  Apoptosis
ko05202  Transcriptional misregulation in cancer

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