Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells

被引:444
作者
Liu, XQ [1 ]
Erikson, RL [1 ]
机构
[1] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA
关键词
D O I
10.1073/pnas.1031523100
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
Elevated expression of mammalian polo-like kinase (PIk)1 occurs in many different types of cancers, and PIk1 has been proposed as a novel diagnostic marker for several tumors. We used the recently developed vector-based small interfering RNA technique to specifically deplete PIk1 in cancer cells. We found that PIk1 depletion dramatically inhibited cell proliferation, decreased viability, and resulted in cell-cycle arrest with 4 N DNA content. The formation of dumbbell-like chromatin structure suggests the inability of these cells to completely separate the sister chromatids at the onset of anaphase. PIk1 depletion induced apoptosis, as indicated by the appearance of subgenomic DNA in fluorescence-activated cell-sorter (FACS) profiles, the activation of caspase 3, and the formation of fragmented nuclei. PIk1-depletion-induced apoptosis was partially reversed by cotransfection of nondegradable mouse PIk1 constructs. In addition, the p53 pathway was shown to be involved in PIk1-depletion-induced apoptosis. DNA damage occurred in PIk1-depleted cells and inhibition of ATM strongly potentiated the lethality of PIk1 depletion. Although p53 is stabilized in PIk1-depleted cells, DNA damage also occurs in p53(-/-) cells. These data support the notion that disruption of PIk1 function could be an important application in cancer therapy.
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页码:5789 / 5794
页数:6
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