Regulation of epidermal growth factor receptor expression in normal and transformed keratinocytes

Summary Transformed keratinocytes (SCC-4, SCC-15, SCC-12F2, SVK14) or normal keratinocytes which differ in their differentiation programme were used to study the regulation of EGF-receptor expression. The capacity of the cells to differentiate was modulated by changing the extracellular calcium concentration. We were able to demonstrate that EGF-receptor expression in normal and transformed keratinocytes depends upon the cell type and one or more levels of regulatory control. At the DNA level, EGF-receptor gene amplification occurred in poorly differentiating cells. At the mRNA level, cells showing EGF-receptor gene amplification expressed elevated mRNA and protein levels when cultured under low Ca²⁺ conditions. Cells not exhibiting EGF-receptor gene amplification showed equal mRNA expression, regardless the Ca²⁺ concentration in the culture medium. At the protein level, EGF-receptor protein was decreased in cells exhibiting EGF-receptor gene amplification when extracellular Ca²⁺ was increased (to 1.6 mM) to stimulate differentiation, the decrease in protein being comparable to mRNA expression. Cells not exhibiting EGF-receptor gene amplification showed equal protein expression, regardless of the Ca²⁺ concentration in the culture medium. Under the same conditions, SV40 transformed keratinocytes showed equal mRNA but elevated protein expression in cells grown under low Ca²⁺ conditions. At the membrane level, normal keratinocytes and SCC-12F2 cells showed elevated numbers of cell surface exposed EGF-receptors in cells grown under low Ca²⁺ conditions, but equal mRNA and protein expression. These and previous findings demonstrate that EGF-receptor expression is regulated at the levels of DNA, mRNA and protein as well as by the plasma membrane composition, depending upon the cell type.