Nerve growth factor-induced alteration in the response of PC12 pheochromocytoma cells to epidermal growth factor

Abstract

PC12 cells, which differentiate morphologically and biochemically into sympathetic neuronlike cells in response to nerve growth factor, also respond to epidermal growth factor. The response to epidermal growth factor is similar in certain respects to the response to nerve growth factor. Both peptides produce rapid increases in cellular adhesion and 2-deoxyglucose uptake and both induce ornithine decarboxylase. But nerve growth factor causes a decreased cell proliferation and a marked hypertrophy of the cells. In contrast, epidermal growth factor enhances cell proliferation and does not cause hypertrophy. Nerve growth factor induces the formation of neurites; epidermal growth factor does not. When both factors are presented simultaneously, the cells form neurites. Furthermore, the biological response to epidermal growth factor, as exemplified by the induction of ornithine decarboxylase, is attenuated by prior treatment of the cells with nerve growth factor. PC12 cells have epidermal growth factor receptors. The binding of epidermal growth factor to these receptors is rapid and specific, and exhibits an equilibrium constant of 1.9 x 10-9 M. Approximately 80,000 receptors are present per cell, and this number is independent of cell density. Treatment of the cells with nerve growth factor reduces the amount of epidermal growth factor binding by at least 80%. The decrease in receptor binding begins after ~12-18 h of nerve growth factor treatment and is complete within 3 d. Scatchard plots indicate that the number of binding sites decreases, not the affinity of the binding sites for epidermal growth factor.