Deoxyribonucleic acid-binding ability of androgen receptors in whole cells: implications for the actions of androgens and antiandrogens

Endocrinology
C W Kuil, E Mulder

Abstract

In whole cells, the effects of several androgens and antiandrogens on the in the induction of DNA binding for the human wild-type androgen receptor (AR) and a mutant receptor ARL (LNCaP mutation; codon 868, Thr to Ala) were examined and related to the transcription activation ability of these receptors. To study DNA binding, an AR expression vector was cotransfected in Chinese hamster ovary cells with a promoter interference plasmid cytomegalovirus-(androgen-responsive element)3-luciferase, containing one or more androgen-responsive elements between the TATA box of the cytomegalovirus promoter and the start site of luciferase gene transcription. Expression levels of the AR are up-regulated by some agonists, but receptor expression levels are comparable for all antiandrogens studied. In the presence of androgens, the wild-type AR is able to reduce promoter activity of the cytomegalovirus-(androgen-responsive element)3-luciferase plasmid, indicating androgen-dependent DNA binding of the AR. The full antagonists hydroxyflutamide, ICI 176.334, and RU 23908 block AR binding to DNA. The antagonists cyproterone acetate and RU 38486 induce approximately 50% of the DNA binding found for androgens. In a transcription activation assay, th...Continue Reading

Citations

Apr 4, 2003·Proceedings of the National Academy of Sciences of the United States of America·Hiroshi MiyamotoChawnshang Chang
Mar 17, 2000·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·M S OjedaM S Gimenez
Mar 4, 2000·International Journal of Urology : Official Journal of the Japanese Urological Association·H Miyamoto, C Chang
Aug 11, 1998·Circulation·J D MarshR J Schiebinger
Jun 28, 2005·International Journal of Cancer. Journal International Du Cancer·Hiroshi MiyamotoHenry Lardy

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