...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Identification of IGF2 signaling through phosphoinositide-3-kinase regulatory subunit 3 as a growth-promoting axis in glioblastoma
【24h】

Identification of IGF2 signaling through phosphoinositide-3-kinase regulatory subunit 3 as a growth-promoting axis in glioblastoma

机译：通过磷酸肌醇-3-激酶调节亚基3作为胶质母细胞瘤的生长促进轴来鉴定IGF2信号

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

Amplification or overexpression of growth factor receptors is a frequent occurrence in malignant gliomas. Using both expression profiling and in situ hybridization, we identified insulin-like growth factor 2 (IGF2) as a marker for a subset of glioblastomas (GBMs) that lack amplification or overexpression of EGF receptor. Among 165 primary high-grade astrocytomas, 13% of grade Ⅳ tumors and 2% of grade Ⅲ tumors expressed IGF2 mRNA levels > 50-fold the sample population median. IGF2-overexpressing tumors frequently displayed PTEN loss, were highly proliferative, exhibited strong staining for phospho-Akt, and belonged to a subclass of GBMs characterized by poor survival. Using a serum-free culture system, we discovered that IGF2 can substitute for EGF to support the growth of GBM-derived neurospheres. The growth-promoting effects of IGF2 were mediated by the insulin-like growth factor receptor 1 and phospho-inositide-3-kinase regulatory subunit 3 (PIK3R3), a regulatory subunit of phosphoinositide 3-kinase that shows genomic gains in some highly proliferative GBM cases. PIK3R3 knockdown inhibited IGF2-induced growth of GBM-derived neurospheres. The current results provide evidence that the IGF2-PIK3R3 signaling axis is involved in promoting the growth of a subclass of highly aggressive human GBMs that lack EGF receptor amplification. Our data underscore the importance of the phosphoinositide 3-kinase/Akt pathway for growth of high-grade gliomas and suggest that multiple molecular alterations that activate this signaling cascade may promote tumor-igenesis. Further, these findings highlight the parallels between growth factors or receptors that are overexpressed in GBMs and those that support in vitro growth of tumor-derived stem-like cells.
机译：生长因子受体的扩增或过表达在恶性神经胶质瘤中经常发生。使用表达谱分析和原位杂交，我们确定胰岛素样生长因子2（IGF2）作为胶质母细胞瘤（GBMs）缺乏扩增或EGF受体过表达的子集的标志物。在165例原发性高级别星形细胞瘤中，有13％的Ⅳ级肿瘤和2％的Ⅲ级肿瘤表达的IGF2 mRNA水平>样本中位数的50倍。过度表达IGF2的肿瘤经常显示PTEN缺失，高度增殖，对磷酸化Akt表现出强染色，并且属于以不良生存为特征的GBM的一个亚类。使用无血清培养系统，我们发现IGF2可以代替EGF来支持GBM衍生的神经球的生长。 IGF2的促生长作用由胰岛素样生长因子受体1和磷酸肌醇3激酶调节亚基3（PIK3R3）介导，PIK3R3是磷酸肌醇3激酶的调节亚基，在某些高度增殖的GBM中显示出基因组增益案件。 PIK3R3组合式抑制了IGF2诱导的GBM衍生神经球的生长。当前的结果提供了证据，即IGF2-PIK3R3信号轴参与促进缺乏EGF受体扩增的高度侵袭性人GBM的亚类的生长。我们的数据强调了磷酸肌醇3-激酶/ Akt通路对于高级神经胶质瘤生长的重要性，并表明激活该信号级联反应的多种分子改变可能促进肿瘤的发生。此外，这些发现突显了在GBM中过表达的生长因子或受体与支持肿瘤衍生干细胞体外生长的受体之间的相似性。

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