PATHWAY: mmu05215 Help
Entry
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
BRITE hierarchy
Pathway map
Disease
Organism
Mus musculus (house mouse) [GN:
mmu ]
Gene
11911 Atf4; activating transcription factor 4 [KO:K04374 ]
12015 Bad; BCL2-associated agonist of cell death [KO:K02158 ]
12575 Cdkn1a; cyclin dependent kinase inhibitor 1A [KO:K06625 ]
12576 Cdkn1b; cyclin dependent kinase inhibitor 1B [KO:K06624 ]
12912 Creb1; cAMP responsive element binding protein 1 [KO:K05870 ]
12913 Creb3; cAMP responsive element binding protein 3 [KO:K09048 ]
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 ]
16151 Ikbkg; inhibitor of kappaB kinase gamma [KO:K07210 ]
16178 Il1r2; interleukin 1 receptor, type II [KO:K04387 ]
16653 Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827 ]
16842 Lef1; lymphoid enhancer binding factor 1 [KO:K04492 ]
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 ]
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 ]
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 ]
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 ]
231991 Creb5; cAMP responsive element binding protein 5 [KO:K09047 ]
26427 Creb3l1; cAMP responsive element binding protein 3-like 1 [KO:K09048 ]
52466 Slc46a1; solute carrier family 46, member 1 [KO:K14613 ]
54635 Pdgfc; platelet-derived growth factor, C polypeptide [KO:K05450 ]
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 ]
Compound
C05981 Phosphatidylinositol-3,4,5-trisphosphate
C12270 N-Acetylaspartylglutamate
C16038 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
Reference
Authors
Nelson WG, De Marzo AM, Isaacs WB.
Title
Prostate cancer.
Journal
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
Reference
Authors
Pienta KJ, Bradley D.
Title
Mechanisms underlying the development of androgen-independent prostate cancer.
Journal
Reference
Authors
Feldman BJ, Feldman D.
Title
The development of androgen-independent prostate cancer.
Journal
Reference
Authors
Heinlein CA, Chang C.
Title
Androgen receptor in prostate cancer.
Journal
Reference
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
Reference
Authors
Macri E, Loda M.
Title
Role of p27 in prostate carcinogenesis.
Journal
Reference
Authors
Steers WD.
Title
5alpha-reductase activity in the prostate.
Journal
Reference
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
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
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
Reference
Authors
Squire JA
Title
TMPRSS2-ERG and PTEN loss in prostate cancer.
Journal
Reference
Authors
Adamo P, Ladomery MR
Title
The oncogene ERG: a key factor in prostate cancer.
Journal
Reference
Authors
Burdova A, Bouchal J, Tavandzis S, Kolar Z
Title
TMPRSS2-ERG gene fusion in prostate cancer.
Journal
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
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
Reference
Authors
Bakht MK, Beltran H
Title
Biological determinants of PSMA expression, regulation and heterogeneity in prostate cancer.
Journal
Related pathway
mmu04060 Cytokine-cytokine receptor interaction
mmu04981 Folate transport and metabolism
mmu05202 Transcriptional misregulation in cancer
KO pathway
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