title: Experimental evidence of persistent androgen-receptor-dependency in castration-resistant prostate cancer.
abstract: In the majority of castration-resistant prostate cancer (CRPC), prostate-specific antigen (PSA), product of a gene that is almost exclusively regulated by the androgen receptor (AR), still acts as a serum marker reflecting disease burden, indicating that AR signaling is activated even under castrate level of serum androgen. Accumulated evidence shows that transcriptional ability of AR is activated both in ligand-dependent and -independent manners in CRPC cells. Some androgen-independent sublines derived from originally androgen-dependent LNCaP prostate cancer cells overexpress the AR and PSA, for which silencing the AR gene suppresses cellular proliferation. The overexpression of the AR confers androgen-independent growth ability on androgen-dependent prostate cancer cells. Some patient-derived prostate cancer xenograft lines also acquire castration-resistant growth ability secreting PSA. More recent publications have shown that the AR activated in CRPC cells regulates distinct gene sets from that in androgen-dependent status. This concept provides very important insights in the development of novel anti-prostate cancer drugs such as new generation anti-androgens and CYP17 inhibitors.
authors.affiliation: Department of Urology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan. selecao@kuhp.kyoto-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Inoue
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kamba
authors.forename: Osamu
authors.initials: O
authors.lastname: Ogawa
mesh_terms: D002369:Castration; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen
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