Interferon-induced modulation of epidermal growth factor-stimulated growth of a human breast tumor cell line

We have determined that interferon-alpha (IFN-alpha) and IFN-gamma inhibit the growth of a human breast tumor cell line, S4, in vitro. Cells were more sensitive to the antiproliferative effects of low-dose IFN-gamma than IFN-alpha. As the growth of the S4 cell line is enhanced by epidermal growth factor (EGF), we examined the effect of IFN on EGF-dependent growth of S4 cells. Cells plated in 2.5% serum alone failed to grow. EGF stimulated these cells to grow more than twofold. IFN substantially attenuated the EGF-stimulated growth of S4 cells. Binding of EGF to its receptor was unaffected by pretreatment of cells with IFN-alpha. However, a 24-h exposure of cells to IFN-gamma significantly increased the number of EGF receptors on S4 cells. Internalization of the EGF receptor was unaffected by IFN treatment. Binding remained elevated through 4 days of IFN-gamma exposure. Scatchard analysis of receptor binding data revealed that IFN-gamma increased the number of binding sites without changing the affinity of the receptor for its ligand. These results demonstrate that IFN inhibits EGF-stimulated growth of a breast tumor cell line and suggest that the antiproliferative effect of IFN may be due, in part, to its interaction with growth factor-initiated pathways.