Differential induction of the androgen receptor transcriptional activity by selective androgen receptor coactivators.
Several new androgen receptor (AR) cofactors, associated to the ligand binding domain of AR, have been identified by our group and named AR associated protein (ARA)70, ARA55, and ARA54. Our previous reports have suggested that the cofactor ARA70 can confer the androgenic effect from 17 beta-estradiol (E2) and antiandrogen to AR. It is of interest for us to compare and determine if the specificity of sex hormones and antiandrogens could be modulated by different coactivators. Our results indicate that ARA70 is the best coactivator to confer the androgenic activity on E2. Only ARA70 and ARA55 could increase significantly the androgenic activity of hydroxyflutamide, a widely used antiandrogen for the treatment of prostate cancer. Furthermore, as compared to the relative specificity of these coactivators to AR in the prostate cancer DU145 cells, our results suggest that ARA70 has a relatively higher specificity. Together, our data suggest that the specificity of sex hormones and antiandrogens can be modulated by some selective AR coactivators. These findings may not only help us to better understand the specificity of the sex hormones and antiandrogens, but also to facilitate the development of better antiandrogens or androgens to fight the androgen-related diseases, such as prostate cancer.
George Whipple Laboratory for Cancer Research, Department of Pathology, University of Rochester, NY 14642, USA.
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D000728:Androgens; D006801:Humans; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; D011944:Receptors, Androgen / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000494:pharmacology*; D015534:Trans-Activators / Q000494:pharmacology*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects*
D000728:Androgens; C111382:NCOA4 protein, human; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; D011944:Receptors, Androgen; D016160:Retinoblastoma Protein; D015534:Trans-Activators; D014157:Transcription Factors