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Cyclin E As a Coactivator of the Androgen Receptor

Correspondence to: Makoto Nakanishi, Department of Biochemistry, Nagoya City University Medical School, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Tel:+81-52-853-8145 Fax:+81-52-842-3955 E-mail:mkt-naka{at}med.nagoya-cu.ac.jp.

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.

Key Words: cyclin E, androgen receptor, prostate cancer, coactivator, cell cycle

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