| Entry |
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| Name |
Prostate cancer
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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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| Disease |
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| Reference |
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| Authors |
Nelson WG, De Marzo AM, Isaacs WB. |
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| Title |
Prostate cancer. |
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| Journal |
N Engl J Med 349:366-81 (2003) |
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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. |
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| Title |
The emerging role of the PI3-K-Akt pathway in prostate cancer progression. |
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| Journal |
Prostate Cancer Prostatic Dis 8:108-18 (2005) |
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| Reference |
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| Authors |
Pienta KJ, Bradley D. |
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| Title |
Mechanisms underlying the development of androgen-independent prostate cancer. |
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| Journal |
Clin Cancer Res 12:1665-71 (2006) |
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| Reference |
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| Authors |
Feldman BJ, Feldman D. |
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| Title |
The development of androgen-independent prostate cancer. |
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| Journal |
Nat Rev Cancer 1:34-45 (2001) |
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| Reference |
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| Authors |
Heinlein CA, Chang C. |
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| Title |
Androgen receptor in prostate cancer. |
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| Journal |
Endocr Rev 25:276-308 (2004) |
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| Reference |
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| Authors |
Koivisto P, Kolmer M, Visakorpi T, Kallioniemi OP. |
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| Title |
Androgen receptor gene and hormonal therapy failure of prostate cancer. |
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| Journal |
Am J Pathol 152:1-9 (1998) |
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| Reference |
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| Authors |
Zhao XY, Malloy PJ, Krishnan AV, Swami S, Navone NM, Peehl DM, Feldman D. |
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| Title |
Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor. |
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| Journal |
Nat Med 6:703-6 (2000) |
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| Reference |
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| Authors |
Macri E, Loda M. |
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| Title |
Role of p27 in prostate carcinogenesis. |
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| Journal |
Cancer Metastasis Rev 17:337-44 (1998) |
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| Reference |
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| Authors |
Steers WD. |
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| Title |
5alpha-reductase activity in the prostate. |
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| Journal |
Urology 58:17-24; discussion 24 (2001) |
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| Reference |
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| Authors |
Lin D, Meyer DJ, Ketterer B, Lang NP, Kadlubar FF. |
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| 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. |
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| Journal |
Cancer Res 54:4920-6 (1994) |
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| Reference |
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| Authors |
Grimes CA, Jope RS. |
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| Title |
The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling. |
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| Journal |
Prog Neurobiol 65:391-426 (2001) |
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| KO pathway |
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