title: Cyclin E as a coactivator of the androgen receptor.
abstract: 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.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo 113, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: K
authors.initials: K
authors.lastname: Kohri
authors.forename: E
authors.initials: E
authors.lastname: Ogata
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Ikeda
authors.forename: M
authors.initials: M
authors.lastname: Nakanishi
mesh_terms: 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
chemical_list: D019927:Cyclin E; D008024:Ligands; D011944:Receptors, Androgen; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D005982:Glutathione Transferase