EFFECTS OF CA-REGULATED GENES - INTERFERENCE WITH ANDROGEN RECEPTOR-MEDIATED TRANSACTIVATION BY AP-I PROTEINS(+ MOBILIZATION ON EXPRESSION OF ANDROGEN)

BACKGROUND. The adult prostate is maintained through an equilibrium be tween cell growth and death rates. Androgen deprivation induces an inc rease in inh-acellular Ca++, AP-1 gene expression of androgen-inducibl e genes. METHODS. Northern blot analysis, band-shift assays, and trans ient cotransfection assays were used to study the effects of Ca++ mobi lizer A23187 on gene expression in human prostate cancer cells. RESULT S. A23187 repressed androgen-upregulated mRNAs for prostate-specific a ntigen (PSA) and hKLK2, and rapidly induced mRNA levels for c-fos and c-jun. AP-1 protein-DNA binding activities were elevated after A23187 treatments. Androgen receptor (AR)-mediated induction of chloramphenic ol acetyltransferase (CBT) reporter was repressed by AP-1 proteins. CO NCLUSIONS. The repression of AR-mediated induction of PSA and hKLK2 ge nes by Ca++ mobilizers is due to the interference of AR transactivatio n activity by AP-1 proteins. (C) 1997 Wiley-Liss, Inc.