Regulation of basic fibroblast growth factor expression by transforming growth factor beta in cultured human prostate...

Basic fibroblast growth factor (bFGF) and transforming growth factor beta 1 (TGFbeta1) are potential autocrine growth regulators of the prostatic stroma, and therefore may play a role in the development of benign prostatic hyperplasia (BPH). We reported that TGFbeta1 increased bFGF and bFGF mRNA expression in cultured human prostate stromal cells (PS). The current study extends those studies and investigates the mechanism by which TGFbeta1 upregulates the level of bFGF mRNA. A solution hybridization assay was used to quantitate bFGF mRNA. Treatment of PS for 6 hr with TGFbeta1 (1 ng/ml) maximally stimulated bFGF mRNA expression. TGFbeta2 and TGFbeta3 were similarly active in upregulating bFGF mRNA. TGFbeta1 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 stability indicated that the half-life of bFGF mRNA in TGFbeta1-treated PS was 6.8 hr, as compared to 4.3 hr in untreated cells. The data indicated that posttranscriptional mechanisms that increased message stability were, at least in part, responsible for upregulation of bFGF mRNA by TGFbeta1 in PS. Our studies suggest that growth of the prostatic stroma is regulated by the interaction of members of two families of growth modulators, bFGFand TGFbeta. It remains to be determined if an imbalance in this system in favor of stroma hyperplasia plays a role in the development of BPH.