ALPHA-INTERFERON POTENTIATES EPIDERMAL GROWTH-FACTOR RECEPTOR-MEDIATED EFFECTS ON HUMAN EPIDERMOID CARCINOMA KB CELLS

The molecular mechanisms underlying the growth inhibition of human tum or cells induced by recombinant interferon-alpha (IFN alpha) are mostl y unknown. It has been proposed that this effect could be related to d own-regulation and/or impaired function of peptide growth factor recep tors (PGF-Rs) in tumor cells exposed to IFN alpha. However, we have pr eviously described that IFN alpha-induced growth inhibition of human e pidermoid carcinoma cells is paralleled by up-regulation of epidermal growth factor receptor (EGF-R). Here we report that an increase in EGF -R synthesis is detectable after 3 hr of exposure to cytostatic concen tration of IFN alpha in epidermoid KB tumor cells. In these experiment al conditions IFN alpha does not depress and even potentiates EGF-R fu nction. IFN alpha-treated KB cells retain sensitivity to the cytotoxic activity of the anti-EGF-R 225 monoclonal antibody (MAb), which acts through receptor blockade, and are sensitized to the growth-promoting effect of EGF. EGF-induced tyrosine (tyr) phosphorylation both of tota l cellular protein extracts and of the immunoprecipitated EGF-R is inc reased in IFN alpha-treated cells. We conclude that a cross-talk betwe en IFN alpha and EGF occurs in KB cells since IFN alpha, at cytostatic concentration, potentiates the effects mediated by the EGF-R. (C) 199 5 Wiley-Liss, Inc.