INFLUENCE OF TRANSFORMING GROWTH-FACTOR-BETA-1 AND OTHER GROWTH-FACTORS ON BASIC FIBROBLAST GROWTH-FACTOR LEVEL AND PROLIFERATION OF CULTURED HUMAN PROSTATE-DERIVED FIBROBLASTS

Basic fibroblast growth factor (bFGF) has been identified in the human prostate. The level of bFGF has been reported to be elevated in benign prostatic hyperplasia (BPH), compared with normal prostate, suggesting that the growth factor may play a role in this disease of the prostate. Basic FGF is a mitogen for cultured human prostate-derived fibroblasts (PF). PF also synthesize bFGF, suggesting that growth regulation of these cells may be under autocrine control. The current study was undertaken to identify factors that affect PF proliferation and bFGF expression. Transforming growth factor beta1 (TGF-beta1) inhibited PF proliferation. The inhibition by TGF-beta1 was partially overcome by bFGF but not by epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin-like growth factor type 1 (IGF-1), or insulin. Incubation of PF with TGF-beta1 increased bFGF mRNA and immunoreactive bFGF levels in a dose- and time-dependent fashion. None of the other growth factor studies affected bFGF levels. PF were also found to express TGF-beta1 mRNA, the level of which was increased two- to fivefold by TGF-beta1. These observations suggest that PF proliferation is controlled by the interaction of two different growth factors. It is possible that bFGF/TGF-beta imbalance in favor of cell proliferation promotes prostatic stromal hyperplasia.