TRANSFECTION OF CELLS WITH BASIC FIBROBLAST GROWTH-FACTOR AND KAPOSI FIBROBLAST GROWTH-FACTOR GENES INDUCE RESISTANCE TO AND RECEPTOR MODULATION OF TUMOR-NECROSIS-FACTOR

Tumor necrosis factor (TNF) has been shown to inhibit the growth of some cell types and stimulate the proliferation of others by a mechanism that is not understood, In the present study, we investigated the effect of transfection of NM-3T3 cells with either the basic fibroblast growth factor gene (bFGF) or the kaposi FGF gene (K-fgf) on the growth-modulatory effects of TNF, Our results show that transformation of cells with either gene leads to resistance to the growth-inhibitory effects of TNF. The K-fgf gene was found to be a more potent inducer of cellular resistance than the bFGF gene, The cellular resistance correlated with the inhibition of TNF-induced activation of phospholipase A(2) and downmodulation of TNF receptors, Overall, our results indicate that both K-fgf and bFGF play an important role in suppression of antiproliferative effects of TNF.