Upregulation of epidermal growth factor receptor induced by alpha-interferon in human epidermoid cancer cells

Unregulated or increased expression of epidermal growth factor recep tor (EGF-R) is a common event in neoplastic transformation; modulation of such a receptor by physiological agents could be, therefore, of clinical interest. We have studied the binding ability, the availability at cell surface, and the synthesis of EGF-R in the A431 and KB human epidermoid cancer cell lines after treatment with recombinant a-interferon (IFN-a). After 48 h of treatment, IFN-a induces, in both cell lines, growth inhibition and enhances class I major histocompatibility HLA complex expression, which is a common marker of IFN action. [I25I]EGF total binding assessed after 48 h of treatment with IFN-a shows a dosedependent upregulation of EGF-R binding capacity. Saturation plots of the binding data show that IFN-a treatment does not dramatically alter the affinity of the EGF-R and indicate that IFN-a only increases the number of low affinity receptors. We show that this effect is due to a specific increase in the synthesis of the receptor protein, as assessed by immunoprecipitation of [S]methionine-labeled cell extracts. Electron microscopy analysis has confirmed an increase of EGF-R proteins at cell surface without major changes in the morphology of the cells. Taken together, these results indicate that IFN-a consistently induces both the binding capacity and the synthesis of EGF-R in human epidermoid cancer cells and suggest the use of such a mechanism for new anticancer therapies. © 1991, American Association for Cancer Research. All rights reserved.