Effects of Ca++ mobilization on expression of androgen-regulated genes: Interference with androgen receptor-mediated transactivation by AP-I proteins

BACKGROUND. The adult prostate is maintained through an equilibrium between cell growth and death rates. Androgen deprivation induces an increase in inh-acellular Ca++, AP-1 gene expression of androgen-inducible genes. METHODS. Northern blot analysis, band-shift assays, and transient cotransfection assays were used to study the effects of Ca++ mobilizer A23187 on gene expression in human prostate cancer cells. RESULTS. A23187 repressed androgen-upregulated mRNAs for prostate-specific antigen (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 chloramphenicol acetyltransferase (CBT) reporter was repressed by AP-1 proteins. CONCLUSIONS. The repression of AR-mediated induction of PSA and hKLK2 genes by Ca++ mobilizers is due to the interference of AR transactivation activity by AP-1 proteins. (C) 1997 Wiley-Liss, Inc.