Suppression of antiproliferative effects of tumor necrosis factor by transfection of cells with human platelet-derived growth factor B/c-sis gene

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Abstract
The growth of cells is determined by the balance between growth‐stimulatory and growth‐inhibitory signals. In the present study, we demonstrate that the transfection of NIH 3T3 cells with a platelet‐derived growth factor (PDGF‐B/c‐sis) gene induces resistance to the anticellular effects of tumor necrosis factor (TNF). Human tumor cell lines that express elevated levels of c‐sis (e.g. epidermoid carcinoma, A‐431) are also TNF resistant, whereas those that express no significant levels of this gene (e.g. breast adenocarcinoma, MCF‐7) are TNF sensitive. Transfection of cells with the c‐sis gene leads to down‐modulation of TNF receptors and also a decrease in intracellular glutathione levels. Thus, our results demonstrate that over‐expression of PDGF‐B/c‐sis by certain tumor cells can lead to their protection from the anticellular effects of TNF.