Cyclin E as a coactivator of the androgen receptor.
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.
Yamamoto
A
A
Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113, Japan.
Hashimoto
Y
Y
Kohri
K
K
Ogata
E
E
Kato
S
S
Ikeda
K
K
Nakanishi
M
M
D002460:Cell Line; D019927:Cyclin E / Q000502:physiology*; D005982:Glutathione Transferase / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection
D019927:Cyclin E; D008024:Ligands; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D005982:Glutathione Transferase