Regulation of low-density lipoprotein receptor expression during keratinocyte differentiation

Transformed keratinocytes (i.e., SCC-4, SCC-15, SCC-12F2, SVK14) or normal keratinocytes which differ in their differentiation program, were used to study the regulation of low-density lipoprotein (LDL)-receptor expression. The capacity of the cells to differentiate was modulated by changing the extracellular calcium concentration. We now demonstrate that LDL-receptor expression in normal and transformed keratinocytes depends on the cell type and one or more levels of regulatory control. Cells express elevated mRNA levels when cultured under low Ca++ (proliferating) conditions. In contrast, SV40-transformed keratinocytes express decreased message under similar condition. In addition, LDL-receptor protein is decreased in transformed cells when extracellular Ca++ is increased (1.6 mM) to stimulate differentiation; the decrease in protein is comparable to the decrease in mRNA expression. Under the same conditions, normal keratinocytes show markedly decreased LDL-receptor protein relative to the decrease in mRNA. Incubation with LDL-cholesterol decreases the number of cell surface-exposed LDL-receptors. The LDL-receptor in fibroblasts is regulated differently from SCC-4 cells. The addition of LDL-cholesterol to fibroblasts causes decreased LDL-receptor mRNA and protein expression whereas SCC-4 cells show the opposite effect. The addition of cholesterol in non-lipoprotein form causes decreased LDL-receptor mRNA and protein expression in both cell types. These results suggest another, yet unidentified, regulatory mechanism that affects LDL-receptor expression in these two cell types.