...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell cycle >Enforced expression of p14ARF induces p53-dependent cell cycle arrest but not apoptosis.
【24h】

Enforced expression of p14ARF induces p53-dependent cell cycle arrest but not apoptosis.

机译：p14ARF的强制表达诱导p53依赖性细胞周期阻滞，但不诱导凋亡。

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

Expression of the p14ARF tumour suppressor is induced by hyperproliferative signals produced by RAS, MYC and other oncogenes. p14ARF quenches inappropriate mitogenic signaling by activating the p53 pathway, and the frequent loss of p14ARF in human cancer diminishes the duration and level of the p53 response. Consistent with this role, p14ARF accumulation can induce potent cell cycle arrest, but its role in promoting apoptosis has not been well established. Therefore we investigated the effects of p14ARF on the survival and growth of several human cell types. To avoid the toxicity associated with adenoviral-based vectors, we established inducible expression of p14ARF in p53-intact and p53-deficient human cell lines. As expected, transient and inducible expression of p14ARF induced rapid cell cycle arrest only in tumour cells expressing intact p53. Further, p14ARF expression did not promote apoptosis in primary human fibroblasts, or in any human tumour cell line tested, irrespective of p53 status. Instead, p14ARF expression sensitized cells to apoptosis in the presence of inhibitors of topoisomerase II (adriamycin) and transcription (DRB). Thus, loss of p14ARF would be an important step in the selection of apoptotic resistant tumour cells.
机译：p14ARF肿瘤抑制因子的表达是由RAS，MYC和其他癌基因产生的过度增殖信号诱导的。 p14ARF通过激活p53途径淬灭了不适当的促有丝分裂信号，并且人癌症中p14ARF的频繁丢失减少了p53反应的持续时间和水平。与此作用一致，p14ARF积累可以诱导有效的细胞周期停滞，但其在促进细胞凋亡中的作用尚未得到很好的确立。因此，我们研究了p14ARF对几种人类细胞存活和生长的影响。为避免与基于腺病毒的载体相关的毒性，我们在p53完整和p53缺陷的人类细胞系中建立了p14ARF的诱导型表达。如所预期的，p14ARF的瞬时和诱导表达仅在表达完整p53的肿瘤细胞中诱导快速细胞周期停滞。此外，无论p53的状态如何，p14ARF的表达都不会促进原代人成纤维细胞或任何测试的人肿瘤细胞系的凋亡。取而代之的是，在拓扑异构酶II（阿霉素）和转录（DRB）抑制剂存在下，p14ARF表达使细胞对细胞凋亡敏感。因此，p14ARF的丧失将是选择凋亡抗性肿瘤细胞中的重要步骤。

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