Spindle assembly checkpoint and p53 deficiencies cooperate for tumorigenesis in mice

被引：37

作者：

Chi, Ya-Hui ^{[1
]}

Ward, Jerrold M. ^{[2
]}

Cheng, Lily I. ^{[2
]}

Yasunaga, Junichiro ^{[1
]}

Jeang, Kuan-Teh ^{[1
]}

机构：

[1] NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA

[2] NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, Div Intramural Res,NIH, Bethesda, MD 20892 USA

来源：

INTERNATIONAL JOURNAL OF CANCER | 2009年 / 124卷 / 06期

关键词：

Mad1; Mad2; p53; spindle assembly checkpoint; tumorigenesis; CELL-CYCLE CONTROL; MITOTIC CHECKPOINT; CHROMOSOME INSTABILITY; CANCER PREDISPOSITION; ANEUPLOIDY; MAD2; MUTATION; BUB3; HETEROZYGOSITY; IDENTIFICATION;

D O I：

10.1002/ijc.24094

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The spindle assembly checkpoint (SAC) guards against chromosomal missegregation during mitosis. To investigate the role of SAC in tumor development, mice heterozygously knocked out for the mitotic arrest deficient (Mad) genes Mad1 and/or Mad2 were mated with p53(+/-) mice. Increased tumor frequencies were reproducibly observed in Mad2(+/-)p53(+/-) (88.2%) and Mad1(+/-) Mad2(+/-) p53(+/-) (95.0%) mice compared with p53(+/-) (66.7%) mice. Moreover, 53% of Mad2(+/-) p53(+/-) mice developed lymphomas compared with 11% of p53(+/-) mice. By examining chromosome content, increased loss in diploidy was seen in cells from Mad2(+/-) p53(+/-) versus p53(+/-) mice, correlating loss of SAC function, in a P53(+/-) context, with increased aneuploidy and tumorigenesis. The findings here provide evidence for a cooperative role of Mad1/Mad2 and p53 genes in preventing tumor development. (C) 2008 Wiley-Liss, Inc.

引用

页码：1483 / 1489

页数：7

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