Effects of tumor necrosis factor on cell growth and expression of transferrin receptors in human fibroblasts

Human recombinant tumor necrosis factor (TNF) stimulated the growth of confluent human fibroblasts (FS-4) in the presence of fetal calf serum. Epidermal growth factor (EGF) similarly stimulated cellular growth; however other mitogenic factors such as insulin, fibroblast growth factor, 12-O-tetradecanoyl-phorbol-12-acetate and Ca2+ ionophore A23187 did not. The growth-stimulating action of TNF was not synergistic with the activity of EGF in the presence of serum. TNF induced a rapid increase in the binding of transferrin to the cell surface, followed by a return to the basal level within 5 min. A similar increase in transferrin binding was observed in FS-4 cells exposed to EGF. In contrast, insulin caused a prolonged stimulation of transferrin binding. These results suggest that TNF and EGF generate similar or identical intracellular signals for cellular growth and the regulation of transferrin receptor expression.