Homozygous deletions and point mutations of the Rit1/Bcl11b gene in gamma-ray induced mouse thymic lymphomas.
Allelic loss (LOH) mapping and sequence analysis were conducted for gamma-ray induced mouse thymic lymphomas and a novel tumor suppressor gene, Rit1/Bcl11b, on chromosome 12 was isolated. Bi-allelic changes were found in 17 of the 66 p53-proficient lymphomas with Rit1 LOH but in only 2 of the 54 p53-deficient lymphomas. This suggests an association between the presence of functional p53 and inactivation of the Rit1 gene in the lymphoma development. Introduction of Rit1 into HeLa cells lacking Rit1 expression suppressed cell growth. These results indicate that loss-of-function mutations of Rit1 contribute to mouse lymphomagenesis and possibly to human cancer development.
Wakabayashi
Yuichi
Y
Department of Gene Regulation, Graduate School of Medical and Dental Sciences, Niigata University, Asahimachi 1-757, Niigata 951-8122, Japan.
Inoue
Jun
J
Takahashi
Yoshiaki
Y
Matsuki
Atsushi
A
Kosugi-Okano
Hitomi
H
Shinbo
Toshimitsu
T
Mishima
Yukio
Y
Niwa
Ohtsura
O
Kominami
Ryo
R
D000483:Alleles; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002460:Cell Line; D005260:Female; D005720:Gamma Rays; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D006801:Humans; D019656:Loss of Heterozygosity; D008223:Lymphoma / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D017354:Point Mutation; D013953:Thymus Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics* / Q000502:physiology
D016159:Tumor Suppressor Protein p53; C486776:RIT1 protein, human; C472865:Rit1 protein, mouse; D018631:ras Proteins