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Promotion of agonist activity of antiandrogens by the androgen receptor coactivator, ARA70, in human prostate cancer DU145 cells.

Although hormone therapy with antiandrogens has been widely used for the treatment of prostate cancer, some antiandrogens may act as androgen receptor (AR) agonists that may result in antiandrogen withdrawal syndrome. The molecular mechanism of this agonist response, however, remains unclear. Using mammalian two-hybrid assay, we report that antiandrogens, hydroxyflutamide, bicalutamide (casodex), cyproterone acetate, and RU58841, and other compounds such as genistein and RU486, can promote the interaction between AR and its coactivator, ARA70, in a dose-dependent manner. The chloramphenicol acetyltransferase assay further demonstrates that these antiandrogens and related compounds significantly enhance the AR transcriptional activity by cotransfection of AR and ARA70 in a 1:3 ratio into human prostate cancer DU145 cells. Our results suggest that the agonist activity of antiandrogens might occur with the proper interaction of AR and ARA70 in DU145 cells. These findings may provide a good model to develop better antiandrogens without agonist activity.

Pubmed ID: 9636157


  • Miyamoto H
  • Yeh S
  • Wilding G
  • Chang C


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

June 23, 1998

Associated Grants

  • Agency: NCI NIH HHS, Id: CA68568
  • Agency: NCI NIH HHS, Id: CA71570

Mesh Terms

  • Androgen Antagonists
  • Androgens
  • Anilides
  • Cyproterone Acetate
  • Drug Interactions
  • Flutamide
  • Humans
  • Imidazoles
  • Male
  • Mifepristone
  • Nitriles
  • Nuclear Receptor Coactivators
  • Oncogene Proteins
  • Prostatic Neoplasms
  • Protein Binding
  • Protein Conformation
  • Tosyl Compounds
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Activation
  • Tumor Cells, Cultured