FGF-2 blocks TGF-β1-mediated suppression of Bcl-2 in normal melanocytes

Normal melanocytes require growth support provided by the adjacent basement membrane. In contrast, nevus cells and melanoma cells survive in the dermis, and in vitro on a soft collagen gel. Transforming growth factor-β1 (TGF-β1) produced by melanocytes themselves induces apoptosis in normal melanocytes cultured on collagen gel, an effect that can be counteracted by fibroblast growth factor-2 (FGF-2). The purpose of this study was to investigate the mechanisms by which FGF-2 counteracts the apoptotic signals from TGF-β1 in melanocytes cultured on collagen gel. We report that FGF-2 did not interfere with the signal transduction from the TGF-β1 receptors to SMAD2/3 proteins. Instead, TGF-β1 decreased the level of Bcl-2 in normal melanocytes cultured on collagen get, and FGF-2 reversed the TGF-β1-mediated reduction in the level of Bcl-2. In nevus and melanoma cells, TGF-β1 was unable to induce a decrease in the level of Bcl-2, and treatment with FGF-2 did not cause an increase in the level of Bcl-2 in nevus or melanoma cells. In conclusion, our results suggest that a reduction in the level of the anti-apoptotic Bcl-2 is involved in the execution of apoptosis induced by TGF-β1 in normal melanocytes cultured on collagen gel and that FGF-2 can prevent TGF-β1 from causing this reduction.