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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Loss of cryptochrome reduces cancer risk in p53 mutant mice
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Loss of cryptochrome reduces cancer risk in p53 mutant mice

机译：隐花色素的丢失降低了p53突变小鼠的癌症风险

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摘要

It is commonly thought that disruption of the circadian clock increases the cancer incidence in humans and mice. However, it was found that disruption of the clock by the Cryptochrome (Cry) mutation in mice did not increase cancer rate in the mutant mice even after exposing the animals to ionizing radiation. Therefore, in this study we tested the effect of the Cry mutation on carcinogen-esis in a mouse strain prone to cancer because of a p53 mutation, with the expectation that clock disruption in this sensitized background would further increase cancer risk. Paradoxically, we find that the Cry mutation protects p53 mutant mice from the early onset of cancer and extends their median lifespan ≈50%, in part by sensitizing p53 mutant cells to apoptosis in response to genotoxic stress. These results suggest alternative therapeutic approaches in management of cancers associated with a p53 mutation.
机译：通常认为，昼夜节律时钟的破坏会增加人类和小鼠的癌症发病率。但是，已发现即使在将动物暴露于电离辐射后，小鼠中的隐色（Cry）突变对时钟的破坏也不会增加突变小鼠的癌症发生率。因此，在这项研究中，我们测试了Cry突变对由于p53突变而易患癌症的小鼠品系中致癌性的影响，并期望在这种致敏背景下的时钟中断会进一步增加患癌的风险。矛盾的是，我们发现Cry突变可保护p53突变小鼠免于癌症的发作，并延长其中位寿命≈50％，部分原因是通过响应基因毒性应激使p53突变细胞对细胞凋亡敏感。这些结果表明，在治疗与p53突变相关的癌症方面，还有其他治疗方法。

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  • 作者

    Nuri Ozturk; Jin Hyup Lee; Shobhan Gaddameedhi; Aziz Sancar;

  • 作者单位

    Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599;

    Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599;

    Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599;

    Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    apoptosis; circadian clock; DNA repair;

    机译：细胞凋亡生物钟DNA修复;

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