Tumor promoter modulation of epidermal growth factor- and nerve growth factor-induced adhesion and growth factor binding of PC-12 pheochromocytoma cells.
Nerve growth factor (NGF) has previously been shown to increase the rate of adhesion of PC-12 pheochromocytoma cells to cell culture dishes. This increase in the rate of adhesion was postulated to be important in NGF-mediated neurite outgrowth. We now report that epidermal growth factor (EGF) is also able to increase the rate of adhesion of PC-12 cells to cell culture dishes, but does not elicit neurite outgrowth. The dose-response curve for EGF is bell-shaped, in contrast to the more classically shaped dose-response curve obtained with NGF. Tetradecanoyl-phorbol-acetate (TPA), a potent tumor promoter, blocks the EGF-induced increase in adhesion rate of PC-12 cells, but does not alter the NGF-induced increase in adhesion rate. TPA shifts the EGF bindings curve to the right for PC-12 cells, but does not alter maximal EGF binding at saturating concentrations of EGF. The binding of NGF to PC-12 cells is not affected by TPA. NGF-induced neurite formation by PC-12 cells is unaffected by TPA, in contrast to the previously reported delay of neurite outgrowth of serum-deprived neuroblastoma cells and NGF-exposed chick embryonic ganglia cells. NGF and EGF both cause a decrease in the number of short microvilli and an increase in the number of long microvilli on PC-12 cells. TPA blocks the decrease in the number of short microvilli in EGF-treated cells, but not in NGF-treated cells. Long microvilli formation is blocked by TPA in both conditions, suggesting the latter are not involved in the increased adhesion rates.
D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D008871:Microvilli / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D010673:Pheochromocytoma; D010704:Phorbols / Q000494:pharmacology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D009414:Nerve Growth Factors; D010455:Peptides; D010704:Phorbols; D004815:Epidermal Growth Factor; D013755:Tetradecanoylphorbol Acetate