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• W2158349558 endingPage "1877" @default.
• W2158349558 startingPage "1870" @default.
• W2158349558 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, the RU 38646-bound receptor was almost inactive, and the receptor complexed with cyproterone acetate showed partial agonistic activity. Interaction of the antagonists cyproterone acetate, hydroxyflutamide, and RU 23908 with the mutant receptor ARL resulted in both DNA-bound and a transcriptionally active receptor. In conclusion, transformation of the AR to a DNA-binding state in whole cells is blocked by several antiandrogens. Furthermore, studies with the antiandrogens cyproterone acetate and RU 38486 show that DNA binding alone is not sufficient to accomplish full transcriptional activity. Full activity requires additional changes, presumably in the protein structure of the receptor." @default.
• W2158349558 created "2016-06-24" @default.
• W2158349558 creator A5031294681 @default.
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• W2158349558 date "1996-05-01" @default.
• W2158349558 modified "2023-09-23" @default.
• W2158349558 title "Deoxyribonucleic acid-binding ability of androgen receptors in whole cells: implications for the actions of androgens and antiandrogens." @default.
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• W2158349558 doi "https://doi.org/10.1210/endo.137.5.8612526" @default.
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• W2158349558 hasPublicationYear "1996" @default.
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