...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Lung cancer: Journal of the International Association for the Study of Lung Cancer >Activation of the AKT and STAT3 pathways and prolonged survival by a mutant EGFR in human lung cancer cells.
【24h】

Activation of the AKT and STAT3 pathways and prolonged survival by a mutant EGFR in human lung cancer cells.

机译：一种蛋白激酶的激活和STAT3通路长期生存的表皮生长因子受体突变在人类的肺癌细胞。

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

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

摘要

To clarify the pathogenic and biological significance of EGFR mutations in lung cancer, we compared the status of ERBB family receptors, their downstream signal transductions and biological phenotypes between lung cancer cell lines with mutant and wild type EGFR. We initially analyzed expression and phosphorylation of ERBB family receptors and their major downstream proteins, AKT, p44/42 MAPK and STAT3, in a series of lung cancer cell lines with or without EGFR mutation. The expression levels of EGFR as well as of ERBB2 and ERBB3 proteins in cells with EGFR mutation tended to be higher than those in cells with wild type EGFR. There was no difference in stability between mutant and wild type EGFR proteins. EGF induced phosphorylation of EGFR, AKT, p44/42 MAPK and STAT3 to various extents, but the level of induction was not associated with the existence of EGFR mutation. These results implied that the activation of AKT, p44/42 MAPK and STAT3 signaling transmitted by EGFR would be critical for the growth and survival of lung cancer cells, but specific features of mutant EGFR in lung cancer cells was not discriminated by these approaches. We therefore performed transfection studies using PC-13 cells with no detectable endogenous EGFR expression. Exogenous expression of wild type and mutant EGFR (delE746-A750) in the cells revealed that only in the mutant EGFR transfected cells, EGFR itself as well as AKT and STAT3 were highly phosphorylated after 24h of serum deprivation. The survival time of mutant EGFR transfected cells was prolonged under serum-free culture conditions, but not under standard culture conditions with 10% serum. These results suggest that cells with a mutant EGFR survive through the activation of the AKT and/or STAT3 pathways, even in low EGF microenvironments. This specific property due to EGFR mutation could be an important step of multistage lung cancer progression.
机译：澄清致病性和生物学肺癌表皮生长因子受体突变的意义,我们ERBB家族受体的状态相比,他们的下游信号转导和生物表型之间的肺癌细胞行与突变体和野生型EGFR。最初的分析表达式和磷酸化ERBB家族受体及其重要下游蛋白质,AKT, p44/42 MAPK和STAT3,在一系列的肺癌细胞系或表皮生长因子受体突变。表皮生长因子受体以及ERBB2和ERBB3蛋白质细胞表皮生长因子受体突变往往高于与野生型细胞表皮生长因子受体。不同突变体和野生之间的稳定表皮生长因子受体蛋白质类型。表皮生长因子受体、AKT p44/42 MAPK和STAT3不同区段,但感应没有水平与表皮生长因子受体突变的存在有关。这些结果暗示一种蛋白激酶的激活,p44/42 MAPK和STAT3信号传播增长和表皮生长因子受体是关键肺癌细胞的生存,但具体表皮生长因子受体在肺癌细胞突变的特点通过这些方法不是歧视。因此进行转染研究使用PC-13细胞没有可检测内源性表皮生长因子受体表达式。突变细胞表皮生长因子受体(delE746-A750)透露只有在表皮生长因子受体突变转染细胞,表皮生长因子受体本身以及一种蛋白激酶和STAT3高度磷酸化后24 h血清剥夺。突变EGFR转染的存活时间长期受到血清培养细胞条件,但不低于标准的文化条件为10%血清。突变的细胞表皮生长因子受体通过生存一种蛋白激酶的激活和/或STAT3通路,甚至在较低的表皮生长因子微环境。由于表皮生长因子受体突变可能是一个属性多级肺癌的重要一步进展。

著录项

相似文献

  • 外文文献
  • 中文文献
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