SUPPRESSION OF ANTIPROLIFERATIVE EFFECTS OF TUMOR-NECROSIS-FACTOR BY TRANSFECTION OF CELLS WITH HUMAN PLATELET-DERIVED GROWTH-FACTOR B C-SIS GENE/

The growth of cells is determined by the balance between growth-stimul atory and growth-inhibitory signals, In the present study, we demonstr ate that the transfection of NIH 3T3 cells with a platelet-derived gro wth factor (PDGF-Blc-sis) gene induces resistance to the anticellular effects of tumor necrosis factor (TNF), Human tumor cell lines that ex press elevated levels of c-sis (e.g. epidermoid carcinoma, A-431) are also TNF resistant, whereas those that express no significant levels o f this gene (e.g. breast adenocarcinoma, MCF-7) are TNF sensitive, Tra nsfection of cells with the c-sis gene leads to down-modulation of TNF receptors and also a decrease in intracellular glutathione levels, Th us, our results demonstrate that over-expression of PDGF-Blc-sis by ce rtain tumor cells can lead to their protection from the anticellular e ffects of TNF.