Opposite effects of EGF on involucrin accumulation of A431 keratinocytes and a variant which is not growth-arrested by EGF

Summary The A431 cell line is composed of malignant keratinocytes derived from a vulval epidermo?d carcinoma. These cells have the peculiarity to stop their proliferation when they are treated with physiological concentrations of EGF, which is a mitogen for normal keratinocytes. We reported earlier that EGF induces involucrin accumulation in A431 cells and proposed that the arrest of proliferation triggers differentiation as shown by the induction of this cornified envelope precursor protein. To test this hypothesis, we compared the A431 subclone 15, which is not growth arrested by EGF-treatment, to the parental A431 cells. We found indeed that EGF reduces the involucrin content of clone 15 cells in a dose dependent manner. These opposite effects of EGF on the expression of terminal differentiation marker involucrin in A431 and A431 clone 15 keratinocytes were observed in defined medium as well as in presence of fetal calf serum. Nevertheless, when growth of parental A431 cells was inhibited by treatment with TGF-β or simply when cultures reached confluency, no involucrin accumulation was observed. Therefore growth arrestper se is not directly correlated with the induction of differentiation. Editor's Statement These results in a well-defined model system support the accepted idea that growth arrest is associated with the processes of cell differentiation, but also indicate that growth arrest alone will not lead to differentiation.