Hec1 overexpression hyperactivates the mitotic checkpoint and induces tumor formation in vivo

被引：133

作者：

Diaz-Rodriguez, Elena ^{[1
]}

Sotillo, Rocio ^{[1
]}

Schvartzman, Juan-Manuel ^{[1
]}

Benezra, Robert ^{[1
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Program Canc Biol & Genet, New York, NY 10065 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 43期

基金：

美国国家卫生研究院;

关键词：

aneuploidy; cancer; chromosome instability;

D O I：

10.1073/pnas.0803504105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Hec1 (Highly Expressed in Cancer 1) is one of four proteins of the outer kinetochore Ndc80 complex involved in the dynamic interface between centromeres and spindle microtubules. Its overexpression is seen in a variety of human tumors and correlates with tumor grade and prognosis. We show here that the overexpression of Hec1 in an inducible mouse model results in mitotic checkpoint hyperactivation. As previously observed with overexpression of the Mad2 gene, hyperactivation of the mitotic checkpoint leads to aneuploidy in vitro and is sufficient to generate tumors in vivo that harbor significant levels of aneuploidy. These results underscore the role of chromosomal instability as a result of mitotic checkpoint hyperactivation in the initiation of tumorigenesis.

引用

页码：16719 / 16724

页数：6

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