...
  • 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 >Semaphorin 3B (SEMA3B) induces apoptosis in lung and breast cancer, whereas VEGF165 antagonizes this effect.
【24h】

Semaphorin 3B (SEMA3B) induces apoptosis in lung and breast cancer, whereas VEGF165 antagonizes this effect.

机译：Semaphorin 3B（SEMA3B）诱导肺癌和乳腺癌细胞凋亡，而VEGF165拮抗这一作用。

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

Semaphorin 3B (SEMA3B) is a secreted member of the semaphorin family, important in axonal guidance. We and others have shown that SEMA3B can act as a tumor suppressor by inducing apoptosis either by reexpression in tumor cells or applied as a soluble ligand. The common method of inactivation of SEMA3B is by allele loss and tumor-acquired promoter methylation. We studied the mechanism of SEMA3B-induced tumor cell apoptosis and found that vascular endothelial growth factor (VEGF)(165) significantly decreased the proapoptotic and antimitotic effect of transfected or secreted SEMA3B on lung and breast cancer cells. VEGF(165) binds to neuropilin, receptors for SEMA3B, and we found that SEMA3B competed for binding of (125)I-VEGF(165) to lung and breast cancer cells. We also found that small interfering RNA knockdown of tumor-produced VEGF-A or the use of an anti-VEGF neutralizing antibody (Ab) significantly inhibited tumor cell growth in vitro. By contrast, VEGF(121), a VEGF variant that lacks binding to neuropilin (NP)-1 or NP-2 receptors, was not expressed in tumor cells and had no effect on SEMA3B growth-suppressing activities. In conclusion, we hypothesize that VEGF(165), produced by tumor cells, acts as an autocrine survival factor and that SEMA3B mediates its tumor-suppressing effects, at least in part, by blocking this VEGF autocrine activity.
机译：Semaphorin 3B（SEMA3B）是Semaphorin家族的一个秘密成员，在轴突指导中很重要。我们和其他人已经表明，SEMA3B可以通过在肿瘤细胞中的重新表达或用作可溶性配体来诱导细胞凋亡来充当肿瘤抑制因子。 SEMA3B失活的常见方法是等位基因缺失和肿瘤获得的启动子甲基化。我们研究了SEMA3B诱导肿瘤细胞凋亡的机制，发现血管内皮生长因子（VEGF）（165）显着降低了转染或分泌的SEMA3B对肺癌和乳腺癌细胞的促凋亡和抗有丝分裂作用。 VEGF（165）与SEMA3B受体Neuropilin结合，我们发现SEMA3B竞争（125）I-VEGF（165）与肺癌和乳腺癌细胞的结合。我们还发现，肿瘤产生的VEGF-A的小干扰RNA敲低或抗VEGF中和抗体（Ab）的使用在体外显着抑制了肿瘤细胞的生长。相比之下，VEGF（121）是一种缺乏与神经毛蛋白（NP）-1或NP-2受体结合的VEGF变体，在肿瘤细胞中不表达，对SEMA3B的生长抑制活性没有影响。总之，我们假设肿瘤细胞产生的VEGF（165）充当自分泌生存因子，而SEMA3B至少部分地通过阻断VEGF自分泌活性来介导其肿瘤抑制作用。

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