Loss of transcription factor IRF-1 affects tumor susceptibility in mice carrying the Ha-ras transgene or nullizygosity for p53.
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.
Nozawa
H
H
Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Oda
E
E
Nakao
K
K
Ishihara
M
M
Ueda
S
S
Yokochi
T
T
Ogasawara
K
K
Nakatsuru
Y
Y
Shimizu
S
S
Ohira
Y
Y
Hioki
K
K
Aizawa
S
S
Ishikawa
T
T
Katsuki
M
M
Muto
T
T
Taniguchi
T
T
Tanaka
N
N
D000818:Animals; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000502:physiology*; D005260:Female; D016158:Genes, p53 / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D050856:Interferon Regulatory Factor-1; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis; D009153:Mutagens / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology; D010750:Phosphoproteins / Q000502:physiology*; D013997:Time Factors
D004268:DNA-Binding Proteins; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D009153:Mutagens; D010750:Phosphoproteins; D008769:Methylnitronitrosoguanidine; D002945:Cisplatin