Cooperative assembly of androgen receptor into a nucleoprotein complex that regulates the prostate-specific antigen enhancer

Prostate cancer is characterized by elevated serum levels of prostate-speci fic antigen (PSA), PSA gene expression is controlled by an androgen-respons ive transcriptional enhancer, Our study suggests that formation of a nucleo protein complex, encompassing 170 base pairs of enhancer DNA, mediates andr ogen-responsive PSA enhancer activity. The complex is assembled by cooperat ive binding of androgen receptor to at least four tandem, nonconsensus andr ogen response elements (AREs). Systematic mutagenesis of the AREs demonstra ted that they act synergistically to stimulate androgen receptor-responsive gene expression. We discuss a mechanism whereby a combination of high andr ogen receptor levels in the prostate and low affinity AREs contribute to th e cell type specificity and activity of the enhancer.