Polo-Like Kinase 1 Is Essential for Early Embryonic Development and Tumor Suppression
Polo-Like Kinase 1 Is Essential for Early Embryonic Development and Tumor Suppression
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DOI：
10.1128/mcb.00392-08
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发表时间：
2008-11-15
影响因子：
5.3
通讯作者：
Chen, Junjie
中科院分区：
文献类型：
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作者：
Lu, Lin-Yu;Wood, Jamie L.;Chen, Junjie
Polo-like kinase(Plk)是一种丝氨酸/苏氨酸激酶，在从酵母菌到人类的生物体中高度保守。以往的报道表明，Plk1在有丝分裂的所有阶段都是关键的，并可能在S期的DNA复制中发挥作用。虽然许多工作都集中在Plk1上，但对Plk1在体内的生理功能知之甚少。为了解决这个问题，我们培育了Plk1基因敲除小鼠。PLK1纯合子缺失的小鼠是胚胎致死的，早期Plk1(-/-)胚胎在八细胞阶段后未能存活。免疫细胞化学研究表明，Plk1缺失的胚胎被阻止在有丝分裂阶段之外，这表明Plk1对于正常的细胞周期进程是重要的。由于Plk1在多种肿瘤和肿瘤细胞系中过表达，因此被认为是一种潜在的癌基因。虽然Plk1杂合子出生时是健康的，但这些动物的肿瘤发病率是野生型的三倍，这表明一个Plk1等位基因的丢失会加速肿瘤的形成。总体而言，我们的数据支持Plk1对早期胚胎发育很重要，并可能作为单倍体缺陷的肿瘤抑制因子发挥作用。
Polo-like kinases (Plks) are serine/threonine kinases that are highly conserved in organisms from yeasts to humans. Previous reports have shown that Plk1 is critical for all stages of mitosis and may play a role in DNA replication during S phase. While much work has focused on Plk1, little is known about the physiological function of Plk1 in vivo. To address this question, we generated Plk1 knockout mice. Plk1 homozygous null mice were embryonic lethal, and early Plk1(-/-) embryos failed to survive after the eight-cell stage. Immunocytochemistry studies revealed that Plk1-null embryos were arrested outside the mitotic phase, suggesting that Plk1 is important for proper cell cycle progression. It has been postulated that Plk1 is a potential oncogene, due to its overexpression in a variety of tumors and tumor cell lines. While the Plk1 heterozygotes were healthy at birth, the incidence of tumors in these animals was threefold greater than that in their wild-type counterparts, demonstrating that the loss of one Plk1 allele accelerates tumor formation. Collectively, our data support that Plk1 is important for early embryonic development and may function as a haploinsufficient tumor suppressor.