INTERFERON REGULATORY FACTOR-I IS A MAJOR REGULATOR OF EPIDERMAL GROWTH-FACTOR RECEPTOR GENE-EXPRESSION

Overexpression of the epidermal growth factor receptor (EGFR) occurs i n many; tumors and in breast cancer correlates with poor prognosis for treatment. Here, we report that interferon regulatory factor-1 (IRF-1 ) induces EGFR promoter activity up to 200-fold compared to 3-10-fold induction by other regulators. The region of the promoter that is requ ired for this induction was defined using deletion mutants. In additio n, we found that IRF-1 and tricostatin A, a deacetylase inhibitor, hav e a synergistic effect on EGFR promoter activity. This indicates that the increase in EGFR promoter activity by IRF-1 may also involve chang es in chromatin structure. These results identify IRF-1 as a major reg ulator of EGFR gene expression. (C) 1998 Federation of European Bioche mical Societies.