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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells
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Polo-like kinase (Plk)1 depletion induces apoptosis in cancer cells

机译：Polo样激酶（Plk）1耗竭诱导癌细胞凋亡

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摘要

Elevated expression of mammalian polo-like kinase (Plk)1 occurs in many different types of cancers, and Plk1 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 Plk1 in cancer cells. We found that Plk1 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. Plk1 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. Plk1-depletion-induced apoptosis was partially reversed by cotransfection of nondegradable mouse Plk1 constructs. In addition, the p53 pathway was shown to be involved in Plk1-depletion-induced apoptosis. DNA damage occurred in Plk1-depleted cells and inhibition of ATM strongly potentiated the lethality of Plk1 depletion. Although p53 is stabilized in Plk1-depleted cells, DNA damage also occurs in p53~(-/-) cells. These data support the notion that disruption of Plk1 function could be an important application in cancer therapy.
机译：哺乳动物polo样激酶（Plk）1的表达高表达在许多不同类型的癌症中，Plk1已被提议作为多种肿瘤的新型诊断标记。我们使用了最近开发的基于载体的小干扰RNA技术来专门消耗癌细胞中的Plk1。我们发现Plk1耗竭显着抑制细胞增殖，降低生存能力，并导致细胞周期停滞与4 N DNA含量。哑铃状染色质结构的形成表明这些细胞在后期开始时无法完全分离姐妹染色单体。 Plk1耗竭诱导凋亡，如荧光激活的细胞分选仪（FACS）图谱中亚基因组DNA的出现，胱天蛋白酶3的激活以及核碎片的形成所表明的。通过不可降解的小鼠Plk1构建体的共转染，Plk1耗尽诱导的细胞凋亡被部分逆转。此外，p53通路显示参与Plk1耗尽诱导的细胞凋亡。 DNA损伤发生在Plk1耗尽的细胞中，对ATM的抑制强烈增强了Plk1耗尽的致死性。尽管p53在贫乏Plk1的细胞中稳定，但DNA损伤也发生在p53〜（-/-）细胞中。这些数据支持以下观点：Plk1功能的破坏可能是癌症治疗中的重要应用。

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