• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Oncogene >Oncogene activation in melanocytes links reactive oxygen to multinucleated phenotype and senescence
【24h】

Oncogene activation in melanocytes links reactive oxygen to multinucleated phenotype and senescence

机译：黑色素细胞中的癌基因激活将活性氧与多核表型和衰老联系起来

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Contrary to malignant melanoma, nevi are a benign form of melanocytic hyperproliferation. They are frequently observed as precursor lesions of melanoma, but they also feature biochemical markers of senescence. In particular, evidence for oncogene-induced melanocyte senescence as natural means to prevent tumorigenesis has been obtained in nevi with mutated B-RafV600E. Here, we demonstrate that strong oncogenic growth factor receptor signalling drives melanocytes into senescence, whereas weaker signals keep them in the proliferative state. Activation of oncogene-induced senescence also produces multinucleated giant cells, a long known histological feature of nevus cells. The protein levels of the senescence mediators, p53 and pRB, and their upstream activators do not correlate with senescence. However, strong oncogene signalling leads to pronounced reactive oxygen stress, and scavenging of reactive oxygen species (ROS) efficiently prevents the formation of multinucleated cells and senescence. Similarly, expression of oncogenic N-RAS results in ROS generation, DNA damage and the same multinuclear senescent phenotype. Hence, we identified oncogenic signalling-dependent ROS production as critical mediator of the melanocytic multinuclear phenotype and senescence, both of them being hallmarks of human nevus cells.
机译：与恶性黑色素瘤相反，痣是黑素细胞过度增殖的良性形式。它们经常被视为黑色素瘤的前体病变，但它们也具有衰老的生化标志物。特别地，已经在突变的B-RafV600E的痣中获得了癌基因诱导的黑素细胞衰老作为预防肿瘤发生的天然手段的证据。在这里，我们证明了强大的致癌生长因子受体信号驱动黑素细胞衰老，而较弱的信号则使它们处于增生状态。癌基因诱导的衰老的激活还产生多核巨细胞，这是痣细胞的长期已知组织学特征。衰老介质p53和pRB及其上游激活剂的蛋白质水平与衰老无关。但是，强大的致癌基因信号传导会导致明显的活性氧应激，而活性氧物种（ROS）的清除有效地阻止了多核细胞的形成和衰老。同样，致癌性N-RAS的表达导致ROS的产生，DNA损伤和相同的多核衰老表型。因此，我们确定致癌信号依赖的ROS产生是黑素细胞多核表型和衰老的关键介质，它们都是人痣细胞的标志。

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