REGULATION OF BASIC FIBROBLAST GROWTH-FACTOR EXPRESSION BY TRANSFORMING GROWTH-FACTOR-BETA IN CULTURED HUMAN PROSTATE STROMAL CELLS

Basic fibroblast growth factor (bFGF) and transforming growth factor b eta 1 (TGF beta 1) are potential autocrine growth regulators of the pr ostatic stroma, and therefore may play a role in the development of be nign prostatic hyperplasia (BPH). We reported [Story et al.: Prostate 22:183-197, 1993] that TGF beta 1 increased bFGF and bFGF mRNA express ion in cultured human prostate stromal cells (PS). The current study e xtends those studies and investigates the mechanism by which TGF beta 1 upregulates the level of bFGF mRNA. A solution hybridization assay w as used to quantitate bFGF mRNA. Treatment of PS for 6 hr with TGF bet a 1 (1 ng/ml) maximally stimulated bFGF mRNA expression. TGF beta 2 an d TGF beta 3 were similarly active in upregulating bFGF mRNA. TGF beta 1 or cycloheximide each increased bFGF mRNA about 3-fold. The effect of these agents was not additive. This suggested that a labile protein was involved in processing bFGF mRNA. Determination of message stabil ity indicated that the half-life of bFGF mRNA in TGF beta 1-treated PS was 6.8 hr, as compared to 4.3 hr in untreated cells. The data indica ted that posttranscriptional mechanisms that increased message stabili ty were, at least in part, responsible for upregulation of bFGF mRNA b y TGF beta 1 in PS. Our studies suggest that growth of the prostatic s troma is regulated by the interaction of members of two families of gr owth modulators, bFGF and TGF beta. It remains to be determined if an imbalance in this system in favor of stroma hyperplasia plays a role i n the development of BPH. (C) 1996 Wiley-Liss, Inc.