Loss of transcription factor IRF-1 affects tumor susceptibility in mice carrying the Ha-ras transgene or nullizygosity for p53

The transcription factor IRE-I has been implicated in tumor suppression: IR F-1 suppresses cell transformation and mediates apoptosis in vitro. Here we show that the loss of IRF-1 alleles per se has no effect on spontaneous tu rner development in the mouse but dramatically exacerbates previous tumor p redispositions caused by the c-Ha-ras transgene or by nullizygosity for p53 . Grossly altered tumor spectrum, as compared to p53-null mice, was also ob served in mice lacking both IRE-I and p53, and cells from these mice show s ignificantly higher mutation rate. Our results suggest that IRF-1 is a new member of the tumor susceptibility genes.