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 NIH-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 A2 and down-modulation of TNF receptors. Overall, our results indicate that both K-fgf and bFGF play an important role in suppression of antiproliferative effects of TNF.
Aggarwal
B B
BB
Department of Molecular Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Pocsik
E
E
Totpal
K
K
D016475:3T3 Cells; D000818:Animals; D002452:Cell Count / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000502:physiology; D051519:Fibroblast Growth Factor 4; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000502:physiology; D051379:Mice; D009857:Oncogenes; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D014162:Transfection / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
C496446:Fgf4 protein, mouse; D051519:Fibroblast Growth Factor 4; D011518:Proto-Oncogene Proteins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors; D010741:Phospholipases A; D054467:Phospholipases A2