title: Increased androgen receptor transcription: a cause of castration-resistant prostate cancer and a possible therapeutic target.
abstract: Few effective therapies exist for the treatment of castration-resistant prostate cancer (CRPC). Recent evidence suggests that CRPC may be caused by augmented androgen/androgen receptor (AR) signaling, generally involving AR overexpression. Aberrant androgen/AR signaling associated with AR overexpression also plays a key role in prostate carcinogenesis. Although AR overexpression could be attributed to gene amplification, only 10-20% of CRPCs exhibit AR gene amplification, and aberrant AR expression in the remaining instances of CRPC is thought to be attributed to transcriptional, translational, and post-translational mechanisms. Overexpression of AR at the protein level, as well as the mRNA level, has been found in CRPC, suggesting a key role for transcriptional regulation of AR expression. Since the analysis of the AR promoter region in the 1990s, several transcription factors have been reported to regulate AR transcription. In this review, we discuss the molecules involved in the control of AR gene expression, with emphasis on its transcriptional control by transcription factors in prostate cancer. We also consider the therapeutic potential of targeting AR expression.
authors.affiliation: Department of Urology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shiota
authors.forename: Akira
authors.initials: A
authors.lastname: Yokomizo
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
mesh_terms: D059002:Androgen Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D017211:Treatment Failure
chemical_list: D059002:Androgen Receptor Antagonists; D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D014157:Transcription Factors