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

被引:118
作者
Nozawa, H
Oda, E
Nakao, K
Ishihara, M
Ueda, S
Yokochi, T
Ogasawara, K
Nakatsuru, Y
Shimizu, S
Ohira, Y
Hioki, K
Aizawa, S
Ishikawa, T
Katsuki, M
Muto, T
Taniguchi, T
Tanaka, N [1 ]
机构
[1] Univ Tokyo, Grad Sch Med, Dept Immunol, Tokyo 1130033, Japan
[2] Univ Tokyo, Grad Sch Med, Dept Surg Oncol, Tokyo 1130033, Japan
[3] Univ Tokyo, Grad Sch Med, Dept Pathol, Tokyo 1130033, Japan
[4] Univ Tokyo, Fac Med, Tokyo 1130033, Japan
[5] Univ Tokyo, Dept Dna Biol & Embryo Engn, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan
[6] Cent Inst Expt Anim, Miyamae Ku, Kawasaki, Kanagawa 2160001, Japan
[7] Kumamoto Univ, Fac Med, Inst Mol Embryol & Genet, Kumamoto 8600811, Japan
关键词
IRF-1; c-Ha-ras; p53; tumor susceptibility gene; mutation frequency;
D O I
10.1101/gad.13.10.1240
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The transcription factor IRE-I 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 turner 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 IRE-I 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.
引用
收藏
页码:1240 / 1245
页数:6
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