KEGG PATHWAY: mmu05215

PATHWAY: mmu05215

Entry

mmu05215                    Pathway

Name

Prostate cancer - Mus musculus (house mouse)

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; Cancer: specific types

Pathway map

mmu05215

Prostate cancer

Disease

H00024

Prostate cancer

Organism

Mus musculus (house mouse) [GN:mmu]

Gene

100042625

Gstp-ps; glutathione S-transferase, pi, pseudogene [KO:K23790]

104156

Etv5; ets variant 5 [KO:K15593]

108071

Grm5; glutamate receptor, metabotropic 5 [KO:K04604]

109880

Braf; Braf transforming gene [KO:K04365] [EC:2.7.11.1]

110157

Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]

11651

Akt1; thymoma viral proto-oncogene 1 [KO:K04456] [EC:2.7.11.1]

11652

Akt2; thymoma viral proto-oncogene 2 [KO:K04456] [EC:2.7.11.1]

11835

Ar; androgen receptor [KO:K08557]

11836

Araf; Araf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]

11911

Atf4; activating transcription factor 4 [KO:K04374]

12015

Bad; BCL2-associated agonist of cell death [KO:K02158]

12043

Bcl2; B cell leukemia/lymphoma 2 [KO:K02161]

12371

Casp9; caspase 9 [KO:K04399] [EC:3.4.22.62]

12387

Ctnnb1; catenin beta 1 [KO:K02105]

12443

Ccnd1; cyclin D1 [KO:K04503]

12447

Ccne1; cyclin E1 [KO:K06626]

12448

Ccne2; cyclin E2 [KO:K06626]

12566

Cdk2; cyclin dependent kinase 2 [KO:K02206] [EC:2.7.11.22]

12575

Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625]

12576

Cdkn1b; cyclin dependent kinase inhibitor 1B [KO:K06624]

12675

Chuk; conserved helix-loop-helix ubiquitous kinase [KO:K04467] [EC:2.7.11.10]

12912

Creb1; cAMP responsive element binding protein 1 [KO:K05870]

12913

Creb3; cAMP responsive element binding protein 3 [KO:K09048]

12914

Crebbp; CREB binding protein [KO:K04498] [EC:2.3.1.48]

13555

E2f1; E2F transcription factor 1 [KO:K17454]

13557

E2f3; E2F transcription factor 3 [KO:K06620]

13645

Egf; epidermal growth factor [KO:K04357]

13649

Egfr; epidermal growth factor receptor [KO:K04361] [EC:2.7.10.1]

13866

Erbb2; erb-b2 receptor tyrosine kinase 2 [KO:K05083] [EC:2.7.10.1]

13876

Erg; ETS transcription factor [KO:K09435]

14182

Fgfr1; fibroblast growth factor receptor 1 [KO:K04362] [EC:2.7.10.1]

14183

Fgfr2; fibroblast growth factor receptor 2 [KO:K05093] [EC:2.7.10.1]

14275

Folr1; folate receptor alpha [KO:K13649]

14276

Folr2; folate receptor beta [KO:K13649]

14784

Grb2; growth factor receptor bound protein 2 [KO:K04364]

14816

Grm1; glutamate receptor, metabotropic 1 [KO:K04603]

14869

Gstp2; glutathione S-transferase, pi 2 [KO:K23790]

14870

Gstp1; glutathione S-transferase, pi 1 [KO:K23790]

15461

Hras; Harvey rat sarcoma virus oncogene [KO:K02833]

15516

Hsp90ab1; heat shock protein 90 alpha (cytosolic), class B member 1 [KO:K04079]

15519

Hsp90aa1; heat shock protein 90, alpha (cytosolic), class A member 1 [KO:K04079]

16000

Igf1; insulin-like growth factor 1 [KO:K05459]

16001

Igf1r; insulin-like growth factor I receptor [KO:K05087] [EC:2.7.10.1]

16150

Ikbkb; inhibitor of kappaB kinase beta [KO:K07209] [EC:2.7.11.10]

16151

Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210]

16178

Il1r2; interleukin 1 receptor, type II [KO:K04387]

16333

Ins1; insulin I [KO:K04526]

16334

Ins2; insulin II [KO:K04526]

16653

Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]

16842

Lef1; lymphoid enhancer binding factor 1 [KO:K04492]

17246

Mdm2; transformed mouse 3T3 cell double minute 2 [KO:K06643] [EC:2.3.2.27]

17392

Mmp3; matrix metallopeptidase 3 [KO:K01394] [EC:3.4.24.17]

17395

Mmp9; matrix metallopeptidase 9 [KO:K01403] [EC:3.4.24.35]

18033

Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580]

18035

Nfkbia; nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha [KO:K04734]

18095

Nkx3-1; NK3 homeobox 1 [KO:K09348]

18176

Nras; neuroblastoma ras oncogene [KO:K07828]

18590

Pdgfa; platelet derived growth factor, alpha [KO:K04359]

18591

Pdgfb; platelet derived growth factor, B polypeptide [KO:K17386]

18595

Pdgfra; platelet derived growth factor receptor, alpha polypeptide [KO:K04363] [EC:2.7.10.1]

18596

Pdgfrb; platelet derived growth factor receptor, beta polypeptide [KO:K05089] [EC:2.7.10.1]

18607

Pdpk1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]

18706

Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]

18707

Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]

18708

Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]

18709

Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]

18710

Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]

18791

Plat; plasminogen activator, tissue [KO:K01343] [EC:3.4.21.68]

18792

Plau; plasminogen activator, urokinase [KO:K01348] [EC:3.4.21.73]

19211

Pten; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]

19645

Rb1; RB transcriptional corepressor 1 [KO:K06618]

19697

Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735]

20509

Slc19a1; solute carrier family 19 (folate transporter), member 1 [KO:K14609]

20662

Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]

20663

Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]

20732

Spint1; serine protease inhibitor, Kunitz type 1 [KO:K15619]

208647

Creb3l2; cAMP responsive element binding protein 3-like 2 [KO:K09048]

208677

Creb3l3; cAMP responsive element binding protein 3-like 3 [KO:K09048]

21414

Tcf7; transcription factor 7, T cell specific [KO:K02620]

21415

Tcf7l1; transcription factor 7 like 1 (T cell specific, HMG box) [KO:K04490]

21416

Tcf7l2; transcription factor 7 like 2, T cell specific, HMG box [KO:K04491]

21417

Zeb1; zinc finger E-box binding homeobox 1 [KO:K09299]

21802

Tgfa; transforming growth factor alpha [KO:K08774]

22027

Hsp90b1; heat shock protein 90, beta (Grp94), member 1 [KO:K09487]

22059

Trp53; transformation related protein 53 [KO:K04451]

225884

Gstp3; glutathione S-transferase pi 3 [KO:K23790]

231991

Creb5; cAMP responsive element binding protein 5 [KO:K09047]

23797

Akt3; thymoma viral proto-oncogene 3 [KO:K04456] [EC:2.7.11.1]

23920

Insrr; insulin receptor-related receptor [KO:K05086] [EC:2.7.10.1]

242705

E2f2; E2F transcription factor 2 [KO:K09389]

26395

Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]

26396

Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]

26413

Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]

26417

Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]

26427

Creb3l1; cAMP responsive element binding protein 3-like 1 [KO:K09048]

328572

Ep300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]

50528

Tmprss2; transmembrane protease, serine 2 [KO:K09633] [EC:3.4.21.122]

52466

Slc46a1; solute carrier family 46, member 1 [KO:K14613]

53320

Folh1; folate hydrolase 1 [KO:K14592] [EC:3.4.17.21]

54635

Pdgfc; platelet-derived growth factor, C polypeptide [KO:K05450]

56458

Foxo1; forkhead box O1 [KO:K07201]

56637

Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]

56717

Mtor; mechanistic target of rapamycin kinase [KO:K07203] [EC:2.7.11.1]

71785

Pdgfd; platelet-derived growth factor, D polypeptide [KO:K05450]

74769

Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]

78284

Creb3l4; cAMP responsive element binding protein 3-like 4 [KO:K09048]

94224

Srd5a2; steroid 5 alpha-reductase 2 [KO:K12344] [EC:1.3.1.22]

Compound

C00025

L-Glutamate

C00280

Androstenedione

C00410

Progesterone

C00504

Folate

C00535

Testosterone

C00735

Cortisol

C00762

Cortisone

C00951

Estradiol-17beta

C01042

N-Acetyl-L-aspartate

C01227

Dehydroepiandrosterone

C03917

Dihydrotestosterone

C05981

Phosphatidylinositol-3,4,5-trisphosphate

C07653

Flutamide

C12270

N-Acetylaspartylglutamate

C16038

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine

Reference

PMID:12878745

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

PMID:15724144

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

PMID:16551847

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

PMID:11900250

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

PMID:15082523

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

PMID:10835690

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

PMID:10453277

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

PMID:11750244

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

PMID:11527574

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

PMID:21747944

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

PMID:20478527

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

PMID:19399032

Authors

Squire JA

Title

TMPRSS2-ERG and PTEN loss in prostate cancer.

Journal

Nat Genet 41:509-10 (2009)
DOI:10.1038/ng0509-509