...
  • 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 >The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation.
【24h】

The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation.

机译：ErbB2 / ErbB3异二聚体起着致癌作用：ErbB2需要ErbB3来驱动乳腺肿瘤细胞增殖。

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

ErbB2 is a receptor tyrosine kinase whose activity in normal cells depends on dimerization with another ligand-binding ErbB receptor. In contrast, amplification of c-erbB2 in tumors results in dramatic overexpression and constitutive activation of the receptor. Breast cancer cells overexpressing ErbB2 depend on its activity for proliferation, because treatment of these cells with ErbB2-specific antagonistic antibodies or kinase inhibitors blocks tumor cells in the G1 phase of the cell cycle. Intriguingly, loss of ErbB2 signaling is accompanied by a decrease in the phosphotyrosine content of ErbB3. On the basis of these results, it has been proposed that ErbB3 might be a partner for ErbB2 in promoting cellular transformation. To test this hypothesis and directly examine the role of the "kinase dead" ErbB3, we specifically ablated its expression with a designer transcription factor (E3). By infection of ErbB2-overexpressing breast cancer cells with a retrovirus expressing E3, we show that ErbB3 is an essential partner in the transformation process. Loss of functional ErbB2 or ErbB3 has similar effects on cell proliferation and cell cycle regulators. Furthermore, expression of constitutively active protein kinase B rescues the proliferative block induced as a consequence of loss of ErbB2 or ErbB3 signaling. These results demonstrate that ErbB2 overexpression and activity alone are insufficient to promote breast tumor cell division. Furthermore, we identify ErbB3's role, which is to couple active ErbB2 to the phosphatidylinositol 3-kinase/protein kinase B pathway. Thus, the ErbB2/ErbB3 dimer functions as an oncogenic unit to drive breast tumor cell proliferation.
机译：ErbB2是一种酪氨酸激酶受体，其在正常细胞中的活性取决于与另一个与配体结合的ErbB受体的二聚作用。相反，肿瘤中c-erbB2的扩增导致受体的过度表达和组成性激活。过度表达ErbB2的乳腺癌细胞依赖于其增殖活性，因为用ErbB2特异性拮抗抗体或激酶抑制剂处理这些细胞会阻断肿瘤细胞进入细胞周期的G1期。有趣的是，ErbB2信号的缺失伴随着ErbB3磷酸酪氨酸含量的降低。基于这些结果，已经提出ErbB3可能是ErbB2在促进细胞转化中的伙伴。为了检验此假设并直接检查“激酶死亡” ErbB3的作用，我们使用设计者转录因子（E3）专门消除了其表达。通过用表达E3的逆转录病毒感染过表达ErbB2的乳腺癌细胞，我们表明ErbB3是转化过程中的重要伴侣。功能性ErbB2或ErbB3的丢失对细胞增殖和细胞周期调节剂具有相似的影响。此外，组成型活性蛋白激酶B的表达可挽救因ErbB2或ErbB3信号缺失而诱导的增殖阻滞。这些结果证明，单独的ErbB2过表达和活性不足以促进乳腺肿瘤细胞分裂。此外，我们确定了ErbB3的作用，该作用是将活性ErbB2偶联到磷脂酰肌醇3-激酶/蛋白激酶B途径。因此，ErbB2 / ErbB3二聚体作为致癌单元来驱动乳腺肿瘤细胞增殖。

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