Growth inhibition of hepatoma cells by type I interferons: Modification by mutations in the interferon regulatory factor-1 gene

Interferon regulatory factor-1 is an important transcription factor in the interferon system. We have demonstrated that the growth inhibitory effect of type I interferons on human hepatoma cells correlates with levels of transcription of the interferon regulatory factor-1 gene. In this study we investigated whether mutations in this gene cause different responses to type I interferons. DNA from several human hepatoma cell lines was investigated, and nucleotide sequences of the interferon regulatory factor-1 gene were determined. Several point mutations were detected in intron 8 of the gene, and one was found to cause deletion of BamHI cleavage sites. We found several point mutations in the upstream region of the interferon regulatory factor-1 exon 1, and the luciferase promoter assay demonstrated that these mutations modified its promoter activity. These results suggest that polymorphisms of the interferon regulatory factor-1 gene partially contribute to determining the response of cancer cells to growth inhibitory effect of type I interferons.