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 (JP16/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  
CDKN1B; cyclin-dependent kinase inhibitor 1B (p27, Kip1) [KO:K06624]
1017  
CDK2; cyclin-dependent kinase 2 [KO:K02206] [EC:2.7.11.22]
898  
CCNE1; cyclin E1 [KO:K06626]
9134  
CCNE2; cyclin E2 [KO:K06626]
5925  
RB1; retinoblastoma 1 [KO:K06618]
1869  
E2F1; E2F transcription factor 1 [KO:K17454]
1870  
E2F2; E2F transcription factor 2 [KO:K09389]
1871  
E2F3; E2F transcription factor 3 [KO:K06620]
3630  
INS; insulin [KO:K04526]
5154  
PDGFA; platelet-derived growth factor alpha polypeptide [KO:K04359]
5155  
PDGFB; platelet-derived growth factor beta polypeptide [KO:K17386]
56034  
PDGFC; platelet derived growth factor C [KO:K05450]
80310  
PDGFD; platelet derived growth factor D [KO:K05450]
1950  
EGF; epidermal growth factor [KO:K04357]
7039  
TGFA; transforming growth factor, alpha [KO:K08774]
3479  
IGF1; insulin-like growth factor 1 (somatomedin C) [KO:K05459]
3645  
INSRR; insulin receptor-related receptor [KO:K05086] [EC:2.7.10.1]
5156  
PDGFRA; platelet-derived growth factor receptor, alpha polypeptide [KO:K04363] [EC:2.7.10.1]
5159  
PDGFRB; platelet-derived growth factor receptor, beta polypeptide [KO:K05089] [EC:2.7.10.1]
2260  
FGFR1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]
2263  
FGFR2; fibroblast growth factor receptor 2 [KO:K05093] [EC:2.7.10.1]
1956  
EGFR; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]
2064  
ERBB2; v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 [KO:K05083] [EC:2.7.10.1]
3480  
IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
5290  
PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  
PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  
PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
5294  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
5295  
PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
23533  
PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296  
PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503  
PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
5728  
PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.67 3.1.3.48 3.1.3.16]
5170  
PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
4824  
NKX3-1; NK3 homeobox 1 [KO:K09348]
207  
AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208  
AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000  
AKT3; v-akt murine thymoma viral oncogene homolog 3 [KO:K04456] [EC:2.7.11.1]
842  
CASP9; caspase 9, apoptosis-related cysteine peptidase [KO:K04399] [EC:3.4.22.62]
572  
BAD; BCL2-associated agonist of cell death [KO:K02158]
2308  
FOXO1; forkhead box O1 [KO:K07201]
1026  
CDKN1A; cyclin-dependent kinase inhibitor 1A (p21, Cip1) [KO:K06625]
4193  
MDM2; MDM2 proto-oncogene, E3 ubiquitin protein ligase [KO:K06643] [EC:6.3.2.19]
7157  
TP53; tumor protein p53 [KO:K04451]
2932  
GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
1385  
CREB1; cAMP responsive element binding protein 1 [KO:K05870]
468  
ATF4; activating transcription factor 4 [KO:K04374]
10488  
CREB3; cAMP responsive element binding protein 3 [KO:K09048]
90993  
CREB3L1; cAMP responsive element binding protein 3-like 1 [KO:K09048]
64764  
CREB3L2; cAMP responsive element binding protein 3-like 2 [KO:K09048]
84699  
CREB3L3; cAMP responsive element binding protein 3-like 3 [KO:K09048]
148327  
CREB3L4; cAMP responsive element binding protein 3-like 4 [KO:K09048]
9586  
CREB5; cAMP responsive element binding protein 5 [KO:K09047]
1499  
CTNNB1; catenin (cadherin-associated protein), beta 1, 88kDa [KO:K02105]
1387  
CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033  
EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
6932  
TCF7; transcription factor 7 (T-cell specific, HMG-box) [KO:K02620]
83439  
TCF7L1; transcription factor 7-like 1 (T-cell specific, HMG-box) [KO:K04490]
6934  
TCF7L2; transcription factor 7-like 2 (T-cell specific, HMG-box) [KO:K04491]
51176  
LEF1; lymphoid enhancer-binding factor 1 [KO:K04492]
595  
CCND1; cyclin D1 [KO:K04503]
1147  
CHUK; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]
3551  
IKBKB; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [KO:K07209] [EC:2.7.11.10]
8517  
IKBKG; inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [KO:K07210]
4792  
NFKBIA; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
4790  
NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
5970  
RELA; v-rel avian reticuloendotheliosis viral oncogene homolog A [KO:K04735]
596  
BCL2; B-cell CLL/lymphoma 2 [KO:K02161]
2475  
MTOR; mechanistic target of rapamycin (serine/threonine kinase) [KO:K07203]
2885  
GRB2; growth factor receptor-bound protein 2 [KO:K04364]
6654  
SOS1; son of sevenless homolog 1 (Drosophila) [KO:K03099]
6655  
SOS2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
3265  
HRAS; Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845  
KRAS; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893  
NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
369  
ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
673  
BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
5894  
RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
5604  
MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  
MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
6716  
SRD5A2; steroid-5-alpha-reductase, alpha polypeptide 2 (3-oxo-5 alpha-steroid delta 4-dehydrogenase alpha 2) [KO:K12344] [EC:1.3.1.22]
367  
AR; androgen receptor [KO:K08557]
3320  
HSP90AA1; heat shock protein 90kDa alpha (cytosolic), class A member 1 [KO:K04079]
3326  
HSP90AB1; heat shock protein 90kDa alpha (cytosolic), class B member 1 [KO:K04079]
7184  
HSP90B1; heat shock protein 90kDa beta (Grp94), member 1 [KO:K09487]
354  
KLK3; kallikrein-related peptidase 3 [KO:K01351] [EC:3.4.21.77]
2950  
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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