Epidermal growth factor controls smooth muscle alpha-isoactin expression in BC3H1 cells.
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 alpha-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 alpha-isoactin synthesis by serum deprivation is inhibited by EGF in a dose-dependent manner with a half-maximal effect at 3-5 ng/ml and a maximal inhibition at approximately 30 ng/ml. Northern analysis also shows that EGF blocks the accumulation of alpha-isoactin mRNA normally observed during cell differentiation. Addition of EGF to differentiated cells results in a repression of alpha-isoactin synthesis, a stimulation of beta- and gamma-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 alpha-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.
Wang
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YC
Department of Biochemistry, University of Iowa College of Medicine, Iowa City 55242.
Rubenstein
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PA
D000199:Actins / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D003402:Creatine Kinase / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology / Q000502:physiology; D008934:Mitogens / Q000494:pharmacology; D024510:Muscle Development; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000254:growth & development; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis
D000199:Actins; D007328:Insulin; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D004247:DNA; D003402:Creatine Kinase