The relationship between keratinocyte differentiation capacity, lipid synthesis, plasma membrane composition and epidermal growth factor (EGF) binding has been studied in SCC-12F2 cells and normal keratinocytes. The differentiation capacity of the cells, i.e. ionophore-induced cornified envelope formation, was inhibited by various retinoids and stimulated by hydrocortisone. Retinoids that caused a significant reduction of cornified envelope formation, i.e. retinoic acid and 13-cis-retinoic acid, caused only minor changes in lipid synthesis and plasma membrane composition. Arotinoid ethyl sulfone, having a minor effect on cornified envelope formation, caused a drastic inhibition of cholesterol synthesis, resulting in changes in the plasma membrane composition. Hydrocortisone stimulated cornified envelope formation but had only minor effects on lipid synthesis and plasma membrane composition. Of all retinoids tested, only arotinoid ethyl sulfone caused a drastic increase of EGF binding, while hydrocortisone had no effect. The results presented in this study demonstrate that modulations in keratinocyte differentiation, as induced by retinoids or hydrocortisone, are not accompanied by comparable changes in EGF binding. It is concluded that EGF binding is most likely directly dependent upon the composition and properties of the plasma membrane. The effects of retinoids on EGF binding are thus caused by changes in the composition of the plasma membrane and not by modulation of capacity of cells to differentiate.

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