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.
Chen
J K
JK
Dept. of Physiology, Chang Gung Medical College, Taoyuan, Taiwan, ROC.
Lin
S S
SS
D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D003373:Coumaric Acids / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*
D003373:Coumaric Acids; D007295:Inositol Phosphates; D004815:Epidermal Growth Factor; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases