FGF-2 blocks TGF-beta1-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-beta1 (TGF-beta1) 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-beta1 in melanocytes cultured on collagen gel. We report that FGF-2 did not interfere with the signal transduction from the TGF-beta1 receptors to SMAD2/3 proteins. Instead, TGF-beta1 decreased the level of Bcl-2 in normal melanocytes cultured on collagen gel, and FGF-2 reversed the TGF-beta1-mediated reduction in the level of Bcl-2. In nevus and melanoma cells, TGF-beta1 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-beta1 in normal melanocytes cultured on collagen gel and that FGF-2 can prevent TGF-beta1 from causing this reduction.
von Willebrand
Maria
M
Department of Dermatology, Helsinki University Central Hospital, University of Helsinki, PB160, 00029 HUS, Finland. marie.vonwillebrand@helsinki.fi
Köhler
Klaus
K
Alanko
Tuomo
T
Laiho
Marikki
M
Saksela
Olli
O
D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005782:Gels; D006801:Humans; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism; D009506:Nevus / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D005782:Gels; D019253:Proto-Oncogene Proteins c-bcl-2; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D003094:Collagen