α‐interferon potentiates epidermal growth factor receptor‐mediated effects on human epidermoid carcinoma KB cells

The molecular mechanisms underlying the growth inhibition of human tumor cells induced by recombinant interferon‐α (IFNα) are mostly unknown. It has been proposed that this effect could be related to down‐regulation and/or impaired function of peptide growth factor receptors (PGF‐Rs) in tumor cells exposed to IFNα. However, we have previously described that IFNα‐induced growth inhibition of human epidermoid 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 concentration of IFNα in epidermoid KB tumor cells. In these experimental conditions IFNα does not depress and even potentiates EGF‐R function. IFNα‐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 total cellular protein extracts and of the immunoprecipitated EGF‐R is increased in IFNα‐treated cells. We conclude that a cross‐talk between IFNα and EGF occurs in KB cells since IFNα, at cytostatic concentration, potentiates the effects mediated by the EGF‐R. © 1995 Wiley‐Liss, Inc.