期刊
CELL CYCLE
卷 8, 期 7, 页码 1030-1035出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.8.7.7950
关键词
apoptosis; mitotic catastrophe; monoastral mitosis; dimethylenastron; kinesin spindle protein
类别
Tetraploid cells may constitute a metastable intermediate between normal euploidy and cancer-associated aneuploidy. Tetraploid cells are relatively more resistant against DNA damaging agents and are genetically unstable, due to their tendency towards multipolar, asymmetric division. Therefore, it is important to develop strategies for the selective removal of tetraploid cells. Here, we show that targeting the mitotic kinesin Eg5 (also known as kinesin spindle protein, KSP) by a small interfering RNA (siRNA) or by the pharmacological inhibitor dimethylenastron (DIMEN) kills tetraploid tumor cells more efficiently than their diploid precursors. Cell death occurs after an attempt of monoastral mitosis that, in diploid cells, is followed by a prolonged mitotic arrest and morphological reversion to the interphase, with a 4n DNA content. In contrast, DIMEN-treated tetraploid cells exhibit a shorter mitotic arrest, bipolar or multipolar karyokinesis, followed by apoptosis of the daughter cells, as assessed by fluorescence videomicroscopy of cells that express a histone 2B-GFP fusion construct to monitor their chromosomes. Cell death occurred with hallmarks of apoptosis, namely loss of the mitochondrial transmembrane potential and terminal chromatin compaction. In conclusion, tetraploid cells are particular vulnerable to undergo mitotic catastrophe after genetic or pharmacological inhibition of Eg5.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据