Epidermal growth factor controls smooth muscle α-isoactin expression in BC3H1 cells

Abstract

We have examined the effects of epidermal growth factor (EGF), platelet-derived growth factor, and insulin on the differentiation of a mouse vascular smooth muscle-like cell line, the BC3H1 cells. On the basis of cell morphology and smooth muscle α-isoactin synthesis, we demonstrate that EGF at physiological concentrations prevents the differentiation of these cells, whereas platelet-derived growth factor has no apparent effect. The induction of α-isoactin synthesis by serum deprivation is inhibited by EGF in a dose-depenent manner with a half-maximal effect at 3-5 ng/ml and a maximal inhibition at ~ 30 ng/ml. Northern analysis also shows that EGF blocks the accumulation of α-isoactin mRNA normally observed during cell differentiation. Addition of EGF to differentiated cells results in a repression of α-isoactin synthesis, a stimulation of β- and γ-isoactin synthesis, and the stabilization of the nonmuscle isoactins. The synthesis of creatine phosphokinase, a muscle-specific noncontractile protein, is also regulated by EGF in a similar fashion. Modulation by EGF of α-isoactin expression is not affected by aphidicolin and is therefore independent of its mitogenic effect on these cells. Insulin is not required for observation of the EGF-dependent effects but instead seems to promote differentiation. Our results show that EGF can replace serum in controlling the differentiation of BC3H1 cells.