Cyclin E as a coactivator of the androgen receptor

J Cell Biol. 2000 Aug 21;150(4):873-80. doi: 10.1083/jcb.150.4.873.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cyclin E / physiology*
  • Glutathione Transferase / genetics
  • HeLa Cells
  • Humans
  • Ligands
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Trans-Activators / metabolism*
  • Transfection

Substances

  • Cyclin E
  • Ligands
  • Receptors, Androgen
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Glutathione Transferase