KEGG   PATHWAY: hsa05215Help
Entry
hsa05215                    Pathway                                

Name
Prostate cancer - Homo sapiens (human)
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
hsa05215

All organismsOrtholog table
Disease
H00024  
Prostate cancer
Drug
D00075  
Testosterone (JAN/USP)
D00586  
Flutamide (JP17/USP/INN)
D00961  
Bicalutamide (JAN/USP/INN)
D00965  
Nilutamide (USAN/INN)
D03820  
Dutasteride (JAN/USAN/INN)
D04498  
Idronoxil (USAN/INN)
D10218  
Enzalutamide (JAN/USAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
1027  
K06624 cyclin-dependent kinase inhibitor 1B | (RefSeq) CDKN1B; cyclin dependent kinase inhibitor 1B [KO:K06624]
1017  
K02206 cyclin-dependent kinase 2 [EC:2.7.11.22] | (RefSeq) CDK2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
898  
K06626 cyclin E | (RefSeq) CCNE1; cyclin E1 [KO:K06626]
9134  
K06626 cyclin E | (RefSeq) CCNE2; cyclin E2 [KO:K06626]
5925  
K06618 retinoblastoma-associated protein | (RefSeq) RB1; RB transcriptional corepressor 1 [KO:K06618]
1869  
K17454 transcription factor E2F1 | (RefSeq) E2F1; E2F transcription factor 1 [KO:K17454]
1870  
K09389 transcription factor E2F2 | (RefSeq) E2F2; E2F transcription factor 2 [KO:K09389]
1871  
K06620 transcription factor E2F3 | (RefSeq) E2F3; E2F transcription factor 3 [KO:K06620]
3630  
K04526 insulin | (RefSeq) INS; insulin [KO:K04526]
5154  
K04359 platelet-derived growth factor subunit A | (RefSeq) PDGFA; platelet derived growth factor subunit A [KO:K04359]
5155  
K17386 platelet-derived growth factor subunit B | (RefSeq) PDGFB; platelet derived growth factor subunit B [KO:K17386]
56034  
K05450 platelet derived growth factor C/D | (RefSeq) PDGFC; platelet derived growth factor C [KO:K05450]
80310  
K05450 platelet derived growth factor C/D | (RefSeq) PDGFD; platelet derived growth factor D [KO:K05450]
1950  
K04357 epidermal growth factor | (RefSeq) EGF; epidermal growth factor [KO:K04357]
7039  
K08774 transforming growth factor; transforming growth factor alpha [KO:K08774]
3479  
K05459 insulin-like growth factor 1 | (RefSeq) IGF1; insulin like growth factor 1 [KO:K05459]
3645  
K05086 insulin receptor-related receptor [EC:2.7.10.1] | (RefSeq) INSRR; insulin receptor related receptor [KO:K05086] [EC:2.7.10.1]
5156  
K04363 platelet-derived growth factor receptor alpha [EC:2.7.10.1] | (RefSeq) PDGFRA; platelet derived growth factor receptor alpha [KO:K04363] [EC:2.7.10.1]
5159  
K05089 platelet-derived growth factor receptor beta [EC:2.7.10.1] | (RefSeq) PDGFRB; platelet derived growth factor receptor beta [KO:K05089] [EC:2.7.10.1]
2260  
K04362 fibroblast growth factor receptor 1 [EC:2.7.10.1] | (RefSeq) FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
2263  
K05093 fibroblast growth factor receptor 2 [EC:2.7.10.1] | (RefSeq) FGFR2; fibroblast growth factor receptor 2 [KO:K05093] [EC:2.7.10.1]
1956  
K04361 epidermal growth factor receptor [EC:2.7.10.1] | (RefSeq) EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
2064  
K05083 receptor tyrosine-protein kinase erbB-2 [EC:2.7.10.1] | (RefSeq) ERBB2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]
3480  
K05087 insulin-like growth factor 1 receptor [EC:2.7.10.1] | (RefSeq) IGF1R; insulin like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
5290  
K00922 phosphatidylinositol-4; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  
K00922 phosphatidylinositol-4; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  
K00922 phosphatidylinositol-4; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294  
K00922 phosphatidylinositol-4; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
5295  
K02649 phosphoinositide-3-kinase; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
23533  
K02649 phosphoinositide-3-kinase; phosphoinositide-3-kinase regulatory subunit 5 [KO:K02649]
5296  
K02649 phosphoinositide-3-kinase; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  
K02649 phosphoinositide-3-kinase; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
5728  
K01110 phosphatidylinositol-3; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.67 3.1.3.48 3.1.3.16]
5170  
K06276 3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1] | (RefSeq) PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
4824  
K09348 homeobox protein Nkx-3.1 | (RefSeq) NKX3-1; NK3 homeobox 1 [KO:K09348]
207  
K04456 RAC serine/threonine-protein kinase [EC:2.7.11.1] | (RefSeq) AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  
K04456 RAC serine/threonine-protein kinase [EC:2.7.11.1] | (RefSeq) AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  
K04456 RAC serine/threonine-protein kinase [EC:2.7.11.1] | (RefSeq) AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
842  
K04399 caspase 9 [EC:3.4.22.62] | (RefSeq) CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
572  
K02158 Bcl-2-antagonist of cell death | (RefSeq) BAD; BCL2 associated agonist of cell death [KO:K02158]
2308  
K07201 forkhead box protein O1 | (RefSeq) FOXO1; forkhead box O1 [KO:K07201]
1026  
K06625 cyclin-dependent kinase inhibitor 1A | (RefSeq) CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
4193  
K06643 E3 ubiquitin-protein ligase Mdm2 [EC:2.3.2.27] | (RefSeq) MDM2; MDM2 proto-oncogene [KO:K06643] [EC:2.3.2.27]
7157  
K04451 tumor protein p53 | (RefSeq) TP53; tumor protein p53 [KO:K04451]
2932  
K03083 glycogen synthase kinase 3 beta [EC:2.7.11.26] | (RefSeq) GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
1385  
K05870 cyclic AMP-responsive element-binding protein 1 | (RefSeq) CREB1; cAMP responsive element binding protein 1 [KO:K05870]
468  
K04374 cyclic AMP-dependent transcription factor ATF-4 | (RefSeq) ATF4; activating transcription factor 4 [KO:K04374]
10488  
K09048 cyclic AMP-responsive element-binding protein 3 | (RefSeq) CREB3; cAMP responsive element binding protein 3 [KO:K09048]
90993  
K09048 cyclic AMP-responsive element-binding protein 3 | (RefSeq) CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048]
64764  
K09048 cyclic AMP-responsive element-binding protein 3 | (RefSeq) CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048]
84699  
K09048 cyclic AMP-responsive element-binding protein 3 | (RefSeq) CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048]
148327  
K09048 cyclic AMP-responsive element-binding protein 3 | (RefSeq) CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048]
9586  
K09047 cyclic AMP-responsive element-binding protein 5 | (RefSeq) CREB5; cAMP responsive element binding protein 5 [KO:K09047]
1499  
K02105 catenin beta 1 | (RefSeq) CTNNB1; catenin beta 1 [KO:K02105]
1387  
K04498 E1A/CREB-binding protein [EC:2.3.1.48] | (RefSeq) CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033  
K04498 E1A/CREB-binding protein [EC:2.3.1.48] | (RefSeq) EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
6932  
K02620 transcription factor 7 | (RefSeq) TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
83439  
K04490 transcription factor 7-like 1 | (RefSeq) TCF7L1; transcription factor 7 like 1 [KO:K04490]
6934  
K04491 transcription factor 7-like 2 | (RefSeq) TCF7L2; transcription factor 7 like 2 [KO:K04491]
51176  
K04492 lymphoid enhancer-binding factor 1 | (RefSeq) LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
595  
K04503 cyclin D1 | (RefSeq) CCND1; cyclin D1 [KO:K04503]
1147  
K04467 inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10] | (RefSeq) CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
3551  
K07209 inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10] | (RefSeq) IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
8517  
K07210 inhibitor of nuclear factor kappa-B kinase subunit gamma | (RefSeq) IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
4792  
K04734 NF-kappa-B inhibitor alpha | (RefSeq) NFKBIA; NFKB inhibitor alpha [KO:K04734]
4790  
K02580 nuclear factor NF-kappa-B p105 subunit | (RefSeq) NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  
K04735 transcription factor p65 | (RefSeq) RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
596  
K02161 apoptosis regulator Bcl-2 | (RefSeq) BCL2; BCL2, apoptosis regulator [KO:K02161]
2475  
K07203 serine/threonine-protein kinase mTOR [EC:2.7.11.1] | (RefSeq) MTOR; mechanistic target of rapamycin [KO:K07203] [EC:2.7.11.1]
2885  
K04364 growth factor receptor-binding protein 2 | (RefSeq) GRB2; growth factor receptor bound protein 2 [KO:K04364]
6654  
K03099 son of sevenless | (RefSeq) SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
6655  
K03099 son of sevenless | (RefSeq) SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
3265  
K02833 GTPase HRas | (RefSeq) HRAS; HRas proto-oncogene, GTPase [KO:K02833]
3845  
K07827 GTPase KRas | (RefSeq) KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
4893  
K07828 GTPase NRas | (RefSeq) NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
369  
K08845 A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] | (RefSeq) ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
673  
K04365 B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] | (RefSeq) BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
5894  
K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] | (RefSeq) RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  
K04368 mitogen-activated protein kinase kinase 1 [EC:2.7.12.2] | (RefSeq) MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  
K04369 mitogen-activated protein kinase kinase 2 [EC:2.7.12.2] | (RefSeq) MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  
K04371 mitogen-activated protein kinase 1/3 [EC:2.7.11.24] | (RefSeq) MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
K04371 mitogen-activated protein kinase 1/3 [EC:2.7.11.24] | (RefSeq) MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
6716  
K12344 3-oxo-5-alpha-steroid 4-dehydrogenase 2 [EC:1.3.1.22] | (RefSeq) SRD5A2; steroid 5 alpha-reductase 2 [KO:K12344] [EC:1.3.1.22]
367  
K08557 androgen receptor | (RefSeq) AR; androgen receptor [KO:K08557]
3320  
K04079 molecular chaperone HtpG | (RefSeq) HSP90AA1; heat shock protein 90 alpha family class A member 1 [KO:K04079]
3326  
K04079 molecular chaperone HtpG | (RefSeq) HSP90AB1; heat shock protein 90 alpha family class B member 1 [KO:K04079]
7184  
K09487 heat shock protein 90kDa beta | (RefSeq) HSP90B1; heat shock protein 90 beta family member 1 [KO:K09487]
354  
K01351 semenogelase [EC:3.4.21.77] | (RefSeq) KLK3; kallikrein related peptidase 3 [KO:K01351] [EC:3.4.21.77]
2950  
K00799 glutathione S-transferase [EC:2.5.1.18] | (RefSeq) GSTP1; glutathione S-transferase pi 1 [KO:K00799] [EC:2.5.1.18]
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)
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)
Reference
  Authors
Pienta KJ, Bradley D.
  Title
Mechanisms underlying the development of androgen-independent prostate cancer.
  Journal
Clin Cancer Res 12:1665-71 (2006)
Reference
  Authors
Feldman BJ, Feldman D.
  Title
The development of androgen-independent prostate cancer.
  Journal
Nat Rev Cancer 1:34-45 (2001)
Reference
  Authors
Heinlein CA, Chang C.
  Title
Androgen receptor in prostate cancer.
  Journal
Endocr Rev 25:276-308 (2004)
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)
Reference
  Authors
Macri E, Loda M.
  Title
Role of p27 in prostate carcinogenesis.
  Journal
Cancer Metastasis Rev 17:337-44 (1998)
Reference
  Authors
Steers WD.
  Title
5alpha-reductase activity in the prostate.
  Journal
Urology 58:17-24; discussion 24 (2001)
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)
KO pathway
 

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