期刊
JOURNAL OF CELL BIOLOGY
卷 150, 期 4, 页码 873-879出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.150.4.873
关键词
cyclin E; androgen receptor; prostate cancer; coactivator; cell cycle
类别
Androgens play an important role in the growth of prostate cancer, but the molecular mechanism that underlies development of resistance to antiandrogen therapy remains unknown. Cyclin E has now been shown to increase the transactivation activity of the human androgen receptor (AR) in the presence of its ligand dihydrotestosterone. The enhancement of AR activity by cyclin E was resistant to inhibition by the antiandrogen 5-hydroxyflutamide. Cyclin E was shown to bind directly to the COOH terminus portion of the AB domain of the AR, and to enhance its AF-1 transactivation function. These results suggest that cyclin E functions as a coactivator of the AR, and that aberrant expression of cyclin E in tumors may contribute to persistent activation of AR function, even during androgen ablation therapy.
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