[Critical role for cell cycle regulators in androgen receptor function].
Androgen plays 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 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 persistent activation of AR function, even during androgen ablation therapy.
Akita
H
H
Department of Urology, Nagoya City University Medical School.
Hashimoto
Y
Y
Hibino
M
M
Iizuka
A
A
Kohri
K
K
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D018797:Cell Cycle Proteins / Q000502:physiology*; D002455:Cell Division; D019927:Cyclin E / Q000502:physiology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D018797:Cell Cycle Proteins; D019927:Cyclin E; D011944:Receptors, Androgen