Androgen-Dependent transcriptional regulation of the prostate-specific antigen gene by thyroid hormone 3,5,3'-L-triiodothyronine.
Prostate-specific antigen (PSA) is the most useful biomarker for human prostate cancer and may play a role in prostate tumor biology. Androgens, via their receptors, are the major positive regulators of PSA expression. Recently, we showed that thyroid hormone 3,5,3'-L-triiodothyronine (T3) also increases androgen-dependent PSA expression, even though androgen receptor expression is not affected. This report demonstrates for the first time that there is a functional T3-responsive element (TRE) in the 5'-promoter region of the PSA gene. Mutation of this TRE reduced the T3-enhanced androgenic activation of the PSA promoter. Our study provides direct evidence that the PSA gene is regulated by T3 at the transcriptional level.
Zhu
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Department of Biochemistry and Molecular Biology, Mayo Graduate School, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Young
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D000728:Androgens / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000032:analysis / Q000235:genetics*; D011471:Prostatic Neoplasms; D012333:RNA, Messenger / Q000032:analysis; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology*; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000728:Androgens; D012333:RNA, Messenger; D014284:Triiodothyronine; D017430:Prostate-Specific Antigen