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首页> 外文期刊>Cell cycle >Deficiency in PER proteins has no effect on the rate of spontaneous and radiation-induced carcinogenesis
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Deficiency in PER proteins has no effect on the rate of spontaneous and radiation-induced carcinogenesis

机译：PER蛋白缺乏对自发和辐射诱导的癌变速率没有影响

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摘要

There is a growing body of evidence that components of the circadian clock are involved in modulation of numerous signaling pathways, and that clock deregulation due to environmental or genetic factors contributes to the development of various pathologies, including cancer. Previous work performed in tissue culture and in in vivo mouse models defined mammalian PERIOD proteins as tumor suppressors, although some experimental inconsistencies (the use of mice on mixed genetic background, lack of sexual discrimination) did not allow a definitive conclusion. To address this issue in a systematic way, we performed a detailed analysis comparing the incidence of tumor development after low-dose ionizing radiation in male and female wild-type, Per1-/-, and Per2-/- mice. We showed that in contrast to previous reports deficiency in either Per1 or Per2 genes by itself does not make mice more tumor-prone; moreover, some of the long-term effects of ionizing radiation in Per2-deficient mice are reminiscent more of accelerated aging rather than tumor-prone phenotype. Our histopathological analysis also revealed significant sexual dimorphism both in the rate of radiation-induced tumorigenesis and in the spectrum of tumors developed, which underscores the importance of using sex-matched experimental groups for in vivo studies. Based on our results, we suggest that the role of PER proteins as bone fide tumor suppressors needs to be reevaluated.
机译：越来越多的证据表明，生物钟的组成部分参与了许多信号传导途径的调节，并且由于环境或遗传因素导致的生物钟失调导致了包括癌症在内的各种疾病的发展。在组织培养和体内小鼠模型中进行的先前工作将哺乳动物PERIOD蛋白定义为抑癌基因，尽管某些实验上的矛盾（在混合遗传背景下使用小鼠，缺乏性别歧视）并不能得出明确的结论。为了以系统的方式解决此问题，我们进行了详细的分析，比较了雄性和雌性野生型，Per1-/-和Per2-/-小鼠低剂量电离辐射后肿瘤发展的发生率。与先前的报道相比，我们证明了Per1或Per2基因本身的缺乏并不能使小鼠更容易发生肿瘤。此外，Per2缺陷小鼠中电离辐射的一些长期影响让人联想到加速衰老，而不是易发肿瘤的表型。我们的组织病理学分析还显示，在辐射诱发的肿瘤发生率和所形成的肿瘤范围内，均存在明显的性二态性，这强调了使用性别匹配的实验组进行体内研究的重要性。根据我们的结果，我们建议需要重新评估PER蛋白作为骨肿瘤抑癌剂的作用。

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