KEGG   PATHWAY: ko05215Help
Entry
ko05215                     Pathway                                

Name
Prostate cancer
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; Cancers
BRITE hierarchy
Pathway map
Prostate cancer
ko05215

All organismsOrtholog table
Disease
H00024  
Prostate cancer
Orthology
K06624  
cyclin-dependent kinase inhibitor 1B
K02206  
cyclin-dependent kinase 2 [EC:2.7.11.22]
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:3.4.21.-]
K09435  
transcriptional regulator ERG
K01348  
urokinase plasminogen activator [EC:3.4.21.73]
K01343  
tissue plasminogen activator [EC:3.4.21.68]
K01394  
matrix metalloproteinase-3 (stromelysin 1, progelatinase) [EC:3.4.24.17]
K01403  
matrix metalloproteinase-9 (gelatinase B) [EC:3.4.24.35]
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:2.7.10.1]
K04363  
platelet-derived growth factor receptor alpha [EC:2.7.10.1]
K05089  
platelet-derived growth factor receptor beta [EC:2.7.10.1]
K04362  
fibroblast growth factor receptor 1 [EC:2.7.10.1]
K05093  
fibroblast growth factor receptor 2 [EC:2.7.10.1]
K04361  
epidermal growth factor receptor [EC:2.7.10.1]
K05083  
receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1]
K05087  
insulin-like growth factor 1 receptor [EC:2.7.10.1]
K00922  
phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K02649  
phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K01110  
phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [EC:3.1.3.67 3.1.3.48 3.1.3.16]
K06276  
3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1]
K09348  
homeobox protein Nkx-3.1
K04456  
RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04399  
caspase 9 [EC:3.4.22.62]
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:2.3.2.27]
K04451  
tumor protein p53
K03083  
glycogen synthase kinase 3 beta [EC:2.7.11.26]
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:2.3.1.48]
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:2.7.11.10]
K07209  
inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
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:2.7.11.1]
K04364  
growth factor receptor-binding 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:2.7.11.1]
K04365  
B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  
RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  
mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  
mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  
mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K12344  
3-oxo-5-alpha-steroid 4-dehydrogenase 2 [EC:1.3.1.22]
K08557  
androgen receptor
K04079  
molecular chaperone HtpG
K09487  
heat shock protein 90kDa beta
K01351  
semenogelase [EC:3.4.21.77]
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
  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 (2016)
DOI:10.18632/oncotarget.11355

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