TY - JOUR
T1 - Androgen regulation of 5α-Reductase isoenzymes in prostate cancer
T2 - Implications for prostate cancer prevention
AU - Li, Jin
AU - Ding, Zhiyong
AU - Wang, Zhengxin
AU - Lu, Jing Fang
AU - Maity, Sankar N.
AU - Navone, Nora M.
AU - Logothetis, Christopher J.
AU - Mills, Gordon B.
AU - Kim, Jeri
PY - 2011/12/14
Y1 - 2011/12/14
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=83355168638&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=83355168638&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0028840
DO - 10.1371/journal.pone.0028840
M3 - Article
C2 - 22194926
AN - SCOPUS:83355168638
SN - 1932-6203
VL - 6
JO - PloS one
JF - PloS one
IS - 12
M1 - e28840
ER -