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Polo-Like Kinase 1 Is Essential for Early Embryonic Development and Tumor Suppression

机译：Polo样激酶1是早期胚胎发育和肿瘤抑制所必需的。

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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.
机译：Polo样激酶（Plk）是丝氨酸/苏氨酸激酶，在从酵母到人类的生物中高度保守。先前的报道表明，Plk1对有丝分裂的所有阶段都至关重要，并且可能在S期的DNA复制中起作用。尽管有很多工作集中在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，我们生成了Plk1基因敲除小鼠。 Plk1纯合的无效小鼠具有胚胎致死性，早期的Plk1 ？/？胚胎在八细胞期后无法存活。免疫细胞化学研究表明，Plk1无效的胚胎在有丝分裂期外被捕，这表明Plk1对适当的细胞周期进程很重要。据推测，由于Plk1在多种肿瘤和肿瘤细胞系中过表达，因此是潜在的癌基因。虽然Plk1杂合子出生时是健康的，但这些动物中肿瘤的发生率比野生型动物高三倍，这表明一个Plk1等位基因的缺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，并且可能充当单倍型肿瘤抑制因子。

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