Stimulation or inhibition of A431 cell growth by EGF is directly correlated with receptor tyrosine kinase concentration but not with PLC gamma activity.

EGF-induced hydrolysis of phosphatidylinositol 4, 5, biphosphate was compared in A431 cells with respect to their growth response to EGF. A431 cells which express 4- to 5-fold more EGF receptors than A431-4 cells were growth inhibited, while A431-4 cells were growth stimulated by EGF within the same dose range. Treatment of A431 cells with EGF resulted in a 2-fold increase in cellular IP3 levels and the effect in A431-4 cells was not as obvious. In the presence of tyrosine kinase inhibitor coumaric acid (0.2 approximately 2 microM), A431 cell growth was stimulated, rather than inhibited, by EGF in a dose-dependent manner. In contrast, the stimulation of A431-4 cell growth by EGF was reduced under the same conditions. Furthermore, in the presence of coumaric acid (up to 0.5 microM), EGF-induced production of inositol phosphates in A431 cells was not obviously affected. Taken together, the results suggest that EGF-induced growth inhibition of A431 cells may be due to a quantitative changes of EGF-receptor tyrosine kinase activity in areas other than the recruitment and activation of phosphatidylinositol-specific phospholipase C gamma.