...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Anticancer Research: International Journal of Cancer Research and Treatment >Androgen receptor-mTOR crosstalk is regulated by testosterone availability: implication for prostate cancer cell survival.
【24h】

Androgen receptor-mTOR crosstalk is regulated by testosterone availability: implication for prostate cancer cell survival.

机译：雄激素受体-mTOR的串扰受睾丸激素可用性的调节：对前列腺癌细胞的生存有影响。

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

BACKGROUND: Signaling between androgen receptor (AR) and mTOR may be crucial for prostate cancer cells to endure the low androgen and suboptimal nutrient conditions produced by androgen deprivation therapy. MATERIALS AND METHODS: AR and mTOR cross-talk was examined in LNCaP cells exposed to either high or low testosterone. AR and mTOR activities were modified separately using either siRNA knockdown or specific chemical inhibitor. The biological significance of the reciprocal communication was assessed by susceptibility to glucose deprivation-induced cell death. RESULTS: AR positively regulated mTOR activity in both low and high testosterone levels. TSC1 and TSC2, the two negative regulators of mTOR, may be involved since both were up-regulated by AR knockdown. Sub-baseline mTOR increased AR protein levels. However, this effect only occurred with low testosterone. More cells underwent apoptosis if AR function was inhibited during glucose deprivation, which significantly depressed mTOR activity. CONCLUSION: The compensatory increase of AR function due to a repressed mTOR signal is advantageous for survival. Disrupting this loop at the time of initiation of androgen deprivation therapy may delay, or even prevent, the recurrence of prostate cancer.
机译：背景：雄激素受体（AR）和mTOR之间的信号传递对于前列腺癌细胞忍受雄激素剥夺疗法产生的低雄激素和次优营养状况可能至关重要。材料与方法：在暴露于高或低睾丸激素的LNCaP细胞中检查AR和mTOR串扰。使用siRNA敲低或特异性化学抑制剂分别修饰AR和mTOR活性。通过对葡萄糖剥夺诱导的细胞死亡的敏感性来评估相互交流的生物学意义。结果：AR在低和高睾丸激素水平上均积极调节mTOR活性。可能涉及mTOR的两个负调节剂TSC1和TSC2，因为它们都被AR抑制上调。亚基线mTOR增加AR蛋白水平。但是，这种作用仅在睾丸激素水平低下发生。如果在葡萄糖剥夺过程中AR功能受到抑制，则更多的细胞将发生凋亡，从而显着降低mTOR活性。结论：mTOR信号抑制导致AR功能的代偿性增加有利于生存。在开始雄激素剥夺治疗时破坏此循环可能会延迟甚至阻止前列腺癌的复发。

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