Entry |
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Name |
Prostate cancer - Homo sapiens (human)
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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.
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Class |
Human Diseases; Cancers
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Pathway map |

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Network |
| Mutation-inactivated PTEN to PI3K signaling pathway | | Loss of NKX3-1 to PI3K signaling pathway | | Amplified AR to androgen receptor signaling pathway | | Mutation-activated AR to androgen receptor signaling pathway | | Loss of CDKN1B to p27-cell cycle G1/S |
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Disease |
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Drug |
| Testosterone (JAN/USP) | | Flutamide (JP17/USP/INN) | | Bicalutamide (JAN/USP/INN) | | Nilutamide (USAN/INN) | | Idronoxil (USAN/INN) | | Enzalutamide (JAN/USAN) | | Apalutamide (JAN/INN) |
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Organism |
Homo sapiens (human) [GN: hsa]
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Gene |
| CDKN1B; cyclin dependent kinase inhibitor 1B [KO: K06624] | | | | | | | | RB1; RB transcriptional corepressor 1 [KO: K06618] | | E2F1; E2F transcription factor 1 [KO: K17454] | | E2F2; E2F transcription factor 2 [KO: K09389] | | E2F3; E2F transcription factor 3 [KO: K06620] | | TMPRSS2; transmembrane serine protease 2 [KO: K09633] [EC:3.4.21.-] | | ERG; ERG, ETS transcription factor [KO: K09435] | | | | | | | | | | IL1R2; interleukin 1 receptor type 2 [KO: K04387] | | SPINT1; serine peptidase inhibitor, Kunitz type 1 [KO: K15619] | | ETV5; ETS variant 5 [KO: K15593] | | | | PDGFA; platelet derived growth factor subunit A [KO: K04359] | | PDGFB; platelet derived growth factor subunit B [KO: K17386] | | PDGFC; platelet derived growth factor C [KO: K05450] | | PDGFD; platelet derived growth factor D [KO: K05450] | | EGF; epidermal growth factor [KO: K04357] | | TGFA; transforming growth factor alpha [KO: K08774] | | IGF1; insulin like growth factor 1 [KO: K05459] | | | | PDGFRA; platelet derived growth factor receptor alpha [KO: K04363] [EC: 2.7.10.1] | | PDGFRB; platelet derived growth factor receptor beta [KO: K05089] [EC: 2.7.10.1] | | | | | | | | | | IGF1R; insulin like growth factor 1 receptor [KO: K05087] [EC: 2.7.10.1] | | PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO: K00922] [EC: 2.7.1.153] | | PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO: K00922] [EC: 2.7.1.153] | | PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO: K00922] [EC: 2.7.1.153] | | PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO: K02649] | | PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO: K02649] | | PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO: K02649] | | | | PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO: K06276] [EC: 2.7.11.1] | | NKX3-1; NK3 homeobox 1 [KO: K09348] | | | | | | | | | | BAD; BCL2 associated agonist of cell death [KO: K02158] | | FOXO1; forkhead box O1 [KO: K07201] | | CDKN1A; cyclin dependent kinase inhibitor 1A [KO: K06625] | | | | TP53; tumor protein p53 [KO: K04451] | | | | CREB1; cAMP responsive element binding protein 1 [KO: K05870] | | ATF4; activating transcription factor 4 [KO: K04374] | | CREB3; cAMP responsive element binding protein 3 [KO: K09048] | | CREB3L1; cAMP responsive element binding protein 3 like 1 [KO: K09048] | | CREB3L2; cAMP responsive element binding protein 3 like 2 [KO: K09048] | | CREB3L3; cAMP responsive element binding protein 3 like 3 [KO: K09048] | | CREB3L4; cAMP responsive element binding protein 3 like 4 [KO: K09048] | | CREB5; cAMP responsive element binding protein 5 [KO: K09047] | | CTNNB1; catenin beta 1 [KO: K02105] | | | | | | TCF7; transcription factor 7 [KO: K02620] | | TCF7L1; transcription factor 7 like 1 [KO: K04490] | | TCF7L2; transcription factor 7 like 2 [KO: K04491] | | LEF1; lymphoid enhancer binding factor 1 [KO: K04492] | | | | CHUK; conserved helix-loop-helix ubiquitous kinase [KO: K04467] [EC: 2.7.11.10] | | IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO: K07209] [EC: 2.7.11.10] | | IKBKG; inhibitor of nuclear factor kappa B kinase subunit gamma [KO: K07210] | | NFKBIA; NFKB inhibitor alpha [KO: K04734] | | NFKB1; nuclear factor kappa B subunit 1 [KO: K02580] | | RELA; RELA proto-oncogene, NF-kB subunit [KO: K04735] | | BCL2; BCL2, apoptosis regulator [KO: K02161] | | MTOR; mechanistic target of rapamycin kinase [KO: K07203] [EC: 2.7.11.1] | | GRB2; growth factor receptor bound protein 2 [KO: K04364] | | SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO: K03099] | | SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO: K03099] | | HRAS; HRas proto-oncogene, GTPase [KO: K02833] | | KRAS; KRAS proto-oncogene, GTPase [KO: K07827] | | NRAS; NRAS proto-oncogene, GTPase [KO: K07828] | | ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO: K08845] [EC: 2.7.11.1] | | BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO: K04365] [EC: 2.7.11.1] | | RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO: K04366] [EC: 2.7.11.1] | | MAP2K1; mitogen-activated protein kinase kinase 1 [KO: K04368] [EC: 2.7.12.2] | | MAP2K2; mitogen-activated protein kinase kinase 2 [KO: K04369] [EC: 2.7.12.2] | | | | | | | | AR; androgen receptor [KO: K08557] | | HSP90AA1; heat shock protein 90 alpha family class A member 1 [KO: K04079] | | HSP90AB1; heat shock protein 90 alpha family class B member 1 [KO: K04079] | | HSP90B1; heat shock protein 90 beta family member 1 [KO: K09487] | | | | | | ZEB1; zinc finger E-box binding homeobox 1 [KO: K09299] |
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Compound |
| Androstenedione | | Progesterone | | Testosterone | | Cortisol | | Cortisone | | Estradiol-17beta | | Dehydroepiandrosterone | | Dihydrotestosterone | | Phosphatidylinositol-3,4,5-trisphosphate | | Flutamide | | 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine |
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Reference |
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Authors |
Nelson WG, De Marzo AM, Isaacs WB. |
Title |
Prostate cancer. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Pienta KJ, Bradley D. |
Title |
Mechanisms underlying the development of androgen-independent prostate cancer. |
Journal |
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Reference |
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Authors |
Feldman BJ, Feldman D. |
Title |
The development of androgen-independent prostate cancer. |
Journal |
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Reference |
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Authors |
Heinlein CA, Chang C. |
Title |
Androgen receptor in prostate cancer. |
Journal |
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Reference |
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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 |
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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 |
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Reference |
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Authors |
Macri E, Loda M. |
Title |
Role of p27 in prostate carcinogenesis. |
Journal |
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Reference |
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Authors |
Steers WD. |
Title |
5alpha-reductase activity in the prostate. |
Journal |
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Reference |
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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 |
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Authors |
Grimes CA, Jope RS. |
Title |
The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Squire JA |
Title |
TMPRSS2-ERG and PTEN loss in prostate cancer. |
Journal |
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Reference |
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Authors |
Adamo P, Ladomery MR |
Title |
The oncogene ERG: a key factor in prostate cancer. |
Journal |
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Reference |
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Authors |
Burdova A, Bouchal J, Tavandzis S, Kolar Z |
Title |
TMPRSS2-ERG gene fusion in prostate cancer. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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KO pathway |
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