Spindle assembly checkpoint and p53 deficiencies cooperate for tumorigenesis in mice
Spindle assembly checkpoint and p53 deficiencies cooperate for tumorigenesis in mice
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DOI：
10.1002/ijc.24094
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发表时间：
2009-03-15
影响因子：
6.4
通讯作者：
Jeang, Kuan-Teh
中科院分区：
文献类型：
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作者：
Chi, Ya-Hui;Ward, Jerrold M.;Jeang, Kuan-Teh
纺锤体组装检查点(SAC)在有丝分裂过程中防止染色体的错误分离。为了研究SAC在肿瘤发生中的作用，杂合性剔除了有丝分裂抑制缺陷(Mad)基因Mad1和/或Mad2的小鼠与P53(+/-)小鼠交配。MAD2(+/-)P53(+/-)(88.2%)和MAD1(+/-)MAD2(+/-)P53(+/-)(95.0%)小鼠的肿瘤发生率高于P53(+/-)(66.7%)小鼠。此外，53%的MAD2(+/-)P53(+/-)小鼠发生了淋巴瘤，而P53(+/-)小鼠的这一比例为11%。通过检查染色体含量，在MAD2(+/-)P53(+/-)与P53(+/-)小鼠的细胞中，二倍体丢失增加，这与P53(+/-)背景下SAC功能的丧失相关，与非整倍体和肿瘤发生的增加有关。这一发现为MAD1/MAD2和P53基因在预防肿瘤发展中的协同作用提供了证据。(C)2008年Wiley-Liss，Inc.
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.