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.
Chakravarthy
A
A
Department of Pathology, University of Maryland, Baltimore 21201.
Pollak
M
M
Hamburger
A W
AW
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D011485:Protein Binding; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D007370:Interferon Type I; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor; D007371:Interferon-gamma