1. Androgen regulation of 5α-reductase isoenzymes in prostate cancer: implications for prostate cancer prevention
- Author
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Jing Fang Lu, Christopher J. Logothetis, Nora M. Navone, Zhengxin Wang, Jeri Kim, Gordon B. Mills, Jin Li, Zhiyong Ding, and Sankar N. Maity
- Subjects
Male ,Cholestenone 5 alpha-Reductase ,Transcription, Genetic ,lcsh:Medicine ,Biochemistry ,Prostate cancer ,lcsh:Science ,Promoter Regions, Genetic ,Regulation of gene expression ,Multidisciplinary ,Prostate Cancer ,Prostate Diseases ,Dihydrotestosterone ,Enzymes ,Gene Expression Regulation, Neoplastic ,Isoenzymes ,Oncology ,Organ Specificity ,Receptors, Androgen ,Androgens ,Dactinomycin ,Medicine ,Androgen Response Element ,medicine.drug ,Protein Binding ,Research Article ,medicine.medical_specialty ,medicine.drug_class ,Urology ,Biology ,Response Elements ,Gene Expression Regulation, Enzymologic ,3-Oxo-5-alpha-Steroid 4-Dehydrogenase ,Internal medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,RNA, Messenger ,lcsh:R ,Membrane Proteins ,Prostatic Neoplasms ,Cancers and Neoplasms ,Androgen ,medicine.disease ,Xenograft Model Antitumor Assays ,Androgen receptor ,Genitourinary Tract Tumors ,SRD5A1 ,Endocrinology ,SRD5A2 ,Cancer research ,lcsh:Q - Abstract
The enzyme 5α-reductase, which converts testosterone to dihydrotestosterone (DHT), performs key functions in the androgen receptor (AR) signaling pathway. The three isoenzymes of 5α-reductase identified to date are encoded by different genes: SRD5A1, SRD5A2, and SRD5A3. In this study, we investigated mechanisms underlying androgen regulation of 5α-reductase isoenzyme expression in human prostate cells. We found that androgen regulates the mRNA level of 5α-reductase isoenzymes in a cell type–specific manner, that such regulation occurs at the transcriptional level, and that AR is necessary for this regulation. In addition, our results suggest that AR is recruited to a negative androgen response element (nARE) on the promoter of SRD5A3 in vivo and directly binds to the nARE in vitro. The different expression levels of 5α-reductase isoenzymes may confer response or resistance to 5α-reductase inhibitors and thus may have importance in prostate cancer prevention.
- Published
- 2011