Loss of transcription factor IRF-1 affects tumor susceptibility in mice carrying the Ha-ras transgene or nullizygosity for p53
Hiroaki Nozawa(Central Institute for Experimental Animals), Eisei Oda(Tokyo University of Science), Kazuki Nakao(Tokyo University of Science), Masayuki Ishihara(Central Institute for Experimental Animals), Seiji Ueda(Kumamoto University), Taeko Yokochi(Central Institute for Experimental Animals), K. OGASAWARA(Tokyo University of Science), Yoko Nakatsuru(Tokyo University of Science), S Shimizu(Tokyo University of Science), Yasutaka Ohira(Tokyo University of Science), K Hioki(Tokyo University of Science), Sen‐ichi Aizawa(Central Institute for Experimental Animals), Tetsuya Ishikawa(The University of Tokyo), Motoya Katsuki(The University of Tokyo), Tetsuichiro Muto(Central Institute for Experimental Animals), Tadatsugu Taniguchi(Central Institute for Experimental Animals), Nobuyuki Tanaka(The University of Tokyo)
Cited by 123Open Access
Abstract
The transcription factor IRF-1 has been implicated in tumor suppression: IRF-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 tumor development in the mouse but dramatically exacerbates previous tumor predispositions caused by the c-Ha-ras transgene or by nullizygosity for p53. Grossly altered tumor spectrum, as compared to p53-null mice, was also observed in mice lacking both IRF-1 and p53, and cells from these mice show significantly higher mutation rate. Our results suggest that IRF-1 is a new member of the tumor susceptibility genes.