The relationship between epidermal growth factor receptors and the terminal differentiation of A431 carcinoma cells.

The replication of human epidermoid carcinoma A431 cells is inhibited by epidermal growth factor (EGF), with 5 ng/ml of EGF causing 50% inhibition of cellular proliferation. EGF resistant clones isolated from A431 cells were able to replicate in the presence of 100 ng/ml of EGF. That this insensitivity to EGF was probably due to a decrease in the expression of EGF receptors (EGFR) on the cell surface was shown using an EGFR cDNA probe to detect a 68% to 85% decrease relative to parental cells in the amount of EGFR mRNA in the EGF resistant clones. A corresponding decrease in surface EGFR levels was also detected in EGF resistant clones as measured by 125I-EGF binding. Eighteen percent of A431 cells cultured in serum-free medium for 6 days entered a pathway of terminal differentiation, as expressed by the formation of envelope-competent cells, whereas EGF resistant clones exhibited a considerably greater capacity to mature, even when cultured in serum-containing medium. The findings suggest that the concentration of EGFRs is important for the capacity of epidermal cells to undergo terminal differentiation in vitro.