Regulation of epidermal growth factor receptor in human colon cancer cell lines by interferon α

Abstract

Background and aim: The biology of growth factor receptor expression has implications for receptor specific cancer therapy. In this study, we examined: (a) regulation of epidermal growth factor receptor (EGFR) expression in a panel of 10 human colon cancer cell lines using interferon α (IFN-α); (b) ability of IFN-α to inhibit cell proliferation; and (c) sensitivity of IFN-α pretreated cells to EGF. Methods: Cell proliferation was measured both by crystal violet colorimetric and clonogenic assays. Cell surface, intracellular, and/or total cell protein expression of EGFR was assessed by indirect immunofluorescence flow cytometry and/or fluorescein isothiocyanate (FITC)-EGF binding and internalisation flow cytometric assay. Results: IFN-α treatment upregulated expression of cell surface EGFR in seven of 10 colon cancer cell lines within 16 hours, reaching a peak within 48-96 hours; this was accompanied by transient elevation of intracellular EGFR and marked growth inhibition. IFN-α treated cancer cells were still sensitive to EGF proliferative stimulation. Conclusions: Our results indicate that cytostatic concentrations of IFN-α can enhance cell surface and intracellular EGFR expression in a proportion of human colon cancer cells. The antiproliferative action of IFN-α could not block the signal transduction of the EGF-EGFR pathway. This may have clinical implications for improving treatment based on targeting of EGFR.