Mad2 overexpression promotes aneuploidy and tumorigenesis in mice
Mad2 overexpression promotes aneuploidy and tumorigenesis in mice
复制标题
DOI：
10.1016/j.ccr.2006.10.019
复制
发表时间：
2007-01-01
期刊：
影响因子：
50.3
通讯作者：
Benezra, Robert
中科院分区：
文献类型：
--
作者：
Sotillo, Rocio;Hernando, Eva;Benezra, Robert
Mad2是纺锤体检查点的重要组成部分，其阻断分离酶的激活和姐妹染色单体的溶解，直到微管与着丝粒的附着完成。我们在这里表明，Mad2在转基因小鼠中的过度表达导致各种各样的肿瘤，出现断裂的染色体，后期桥，和整个染色体的获得和损失，以及加速myc诱导的淋巴瘤。此外，与迄今为止研究的大多数癌基因不同，Mad2的持续过表达不是肿瘤维持所必需的。这些结果表明，短暂的Mad2过表达和染色体不稳定性可能是不同癌症亚型的起始和进展中的重要刺激。
Mad2 is an essential component of the spindle checkpoint that blocks activation of Separase and dissolution of sister chromatids until microtubule attachment to kinetochores is complete. We show here that overexpression of Mad2 in transgenic mice leads to a wide variety of neoplasias, appearance of broken chromosomes, anaphase bridges, and whole-chromosome gains and losses, as well as acceleration of myc-induced lymphomagenesis. Moreover, continued overexpression of Mad2 is not required for tumor maintenance, unlike the majority of oncogenes studied to date. These results demonstrate that transient Mad2 overexpression and chromosome instability can be an important stimulus in the initiation and progression of different cancer subtypes.