...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >A dominant role for p53-dependent cellular senescence in radiosensitization of human prostate cancer cells.
【24h】

A dominant role for p53-dependent cellular senescence in radiosensitization of human prostate cancer cells.

机译：p53依赖性细胞衰老在人类前列腺癌细胞放射增敏中的主要作用。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Because p53 inactivation may limit the effectiveness of radiation therapy for localized prostate cancer, it is important to understand how this gene regulates clonogenic survival after an exposure to ionizing radiation. Here, we show that premature cellular senescence is the principal mode of cell death accounting for the radiosensitivity of human prostate cancer cell lines retaining p53 function. Alternative stress response pathways controlled by this tumor suppressor, including cell cycle arrest, DNA damage repair, mitotic catastrophe and apoptosis, contributed significantly less to radiation-induced clonogenic death. Using a dominant negative C-terminal fragment of p53, we present the first evidence that a complete loss of endogenous p53 function is sufficient to limit the irradiation-induced senescence and clonogenic death of prostate cancer cells. Conversely, inheritance of wild-type p53 by prostate cancer cells lacking a functional allele of this gene (i.e., DU145) significantly increases clonogenic death through p53-dependent cellular senescence and apoptotic pathways. Our data provide evidence that mutations of even one p53 allele may be sufficient to alter their clonogenic fate. In addition, they support the idea that the p53 pathway can be used as a specific target for enhancing the radiosensitivity of prostate cancer cells. Activation of p53 by the drug nutlin-3 is shown to be an effective radiosensitizer of prostate cancer cells retaining functional alleles of p53 and this effect was entirely attributable to an increased induction of p53-dependent cellular senescence.
机译：由于p53失活可能会限制局部前列腺癌放射治疗的有效性，因此重要的是要了解该基因在电离放射线照射后如何调节克隆形成存活。在这里，我们表明，过早的细胞衰老是细胞死亡的主要模式，这说明了保留p53功能的人前列腺癌细胞系的放射敏感性。受此肿瘤抑制物控制的其他应激反应途径，包括细胞周期停滞，DNA损伤修复，有丝分裂灾难和细胞凋亡，对辐射诱导的克隆形成性死亡的贡献明显较小。使用p53的显性负性C末端片段，我们提供了第一个证据，即内源性p53功能的完全丧失足以限制辐射诱导的前列腺癌细胞衰老和克隆形成性死亡。相反，缺乏该基因的功能性等位基因的前列腺癌细胞（即DU145）对野生型p53的遗传通过依赖p53的细胞衰老和凋亡途径显着增加了克隆形成性死亡。我们的数据提供了证据，即使是一个p53等位基因的突变也可能足以改变其克隆形成的命运。此外，他们支持p53途径可用作增强前列腺癌细胞放射敏感性的特异性靶标的想法。药物nutlin-3激活p53被证明是保留p53功能等位基因的前列腺癌细胞的有效放射增敏剂，这种作用完全归因于对p53依赖性细胞衰老的诱导增加。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号