Interferon regulatory factor-1 is a major regulator of epidermal growth factor receptor gene expression.
Overexpression of the epidermal growth factor receptor (EGFR) occurs in 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 required for this induction was defined using deletion mutants. In addition, we found that IRF-1 and tricostatin A, a deacetylase inhibitor, have a synergistic effect on EGFR promoter activity. This indicates that the increase in EGFR promoter activity by IRF-1 may also involve changes in chromatin structure. These results identify IRF-1 as a major regulator of EGFR gene expression.
Laboratory of Molecular Biology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Y R
YR
Rubinstein
K N
KN
Proctor
M
M
Bergel
B
B
Murphy
A C
AC
Johnson
D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000502:physiology*; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007372:Interferons / Q000378:metabolism; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D010750:Phosphoproteins; D014157:Transcription Factors; D007372:Interferons; D066246:ErbB Receptors