Mad2 overexpression promotes aneuploidy and tumorigenesis in mice

作者：Sotillo Rocio; Hernando Eva; Diaz Rodriguez Elena; Teruya Feldstein Julie; Cordon Cardo Carlos; Lowe Scott W; Benezra Robert^*

来源：Cancer Cell, 2007, 11(1): 9-23.

DOI：10.1016/j.ccr.2006.10.019

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.

• 出版日期2007-1