Cloning and characterization of a specific coactivator, ARA70, for the androgen receptor in human prostate cells.
The androgen receptor (AR) is a member of the steroid receptor superfamily that plays an important role in male sexual differentiation and prostate cell proliferation. Mutations or abnormal expression of AR in prostate cancer can play a key role in the process that changes prostate cancer from androgen-dependent to an androgen-independent stage. Using a yeast two-hybrid system, we were able to isolate a ligand-dependent AR-associated protein (ARA70), which functions as an activator to enhance AR transcriptional activity 10-fold in the presence of 10(-10) M dihydrotestosterone or 10(-9) M testosterone, but not 10(-6) M hydroxyflutamide in human prostate cancer DU145 cells. Our data further indicated that ARA70 Will only slightly induce the transcriptional activity of other steroid receptors such as estrogen receptor, glucocorticoid receptor, and progesterone receptor in DU145 cells. Together, these data suggest that AR may need a specific coactivator(s) such as ARA70 for optimal androgen activity.
Yeh
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S
Department of Medicine and University of Wisconsin Comprehensive Cancer Center, University of Wisconsin, Madison 53792, USA.
Chang
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C
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms; D012333:RNA, Messenger / Q000096:biosynthesis; D011944:Receptors, Androgen / Q000378:metabolism*; D011987:Receptors, Steroid / Q000096:biosynthesis / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology; D015534:Trans-Activators / Q000096:biosynthesis / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C111382:NCOA4 protein, human; D056918:Nuclear Receptor Coactivators; D015513:Oncogene Proteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011987:Receptors, Steroid; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D013196:Dihydrotestosterone; C014290:hydroxyflutamide; D013739:Testosterone; D005485:Flutamide; D015500:Chloramphenicol O-Acetyltransferase