...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Estrogen Exhibits a Biphasic Effect on Prostate Tumor Growth through the Estrogen Receptor β-KLF5 Pathway
【24h】

Estrogen Exhibits a Biphasic Effect on Prostate Tumor Growth through the Estrogen Receptor β-KLF5 Pathway

机译：雌激素通过雌激素受体β-KLF5途径对前列腺肿瘤的生长产生双相作用。

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

摘要

Estrogens are effective in the treatment of prostate cancer; however, the effects of estrogens on prostate cancer are enigmatic. In this study, we demonstrated that estrogen (17β-estradiol [E2]) has biphasic effects on prostate tumor growth. A lower dose of E2 increased tumor growth in mouse xenograft models using DU145 and PC-3 human prostate cancer cells, whereas a higher dose significantly decreased tumor growth. We found that anchorage-independent apoptosis in these cells was inhibited by E2 treatment. Similarly, in vivo angiogenesis was suppressed by E2. Interestingly, these effects of E2 were abolished by knockdown of either estrogen receptor β (ERβ) or Krüppel-like zinc finger transcription factor 5 (KLF5). Ιn addition, E2 suppressed KLF5-mediated transcription through ERβ, which inhibits proapoptotic FOXO1 and proangiogenic PDGFA expression. Furthermore, we revealed that a nonagonistic ER ligand GS-1405 inhibited FOXO1 and PDGFA expression through the ERβ-KLF5 pathway and regulated prostate tumor growth without ERβ transactivation. Therefore, these results suggest that E2 biphasically modulates prostate tumor formation by regulating KLF5-dependent transcription through ERβ and provide a new strategy for designing ER modulators, which will be able to regulate prostate cancer progression with minimal adverse effects due to ER transactivation.
机译：雌激素可有效治疗前列腺癌;然而，雌激素对前列腺癌的作用是神秘的。在这项研究中，我们证明了雌激素（17β-雌二醇[E2]）对前列腺肿瘤的生长具有双相作用。在使用DU145和PC-3人前列腺癌细胞的小鼠异种移植模型中，较低剂量的E2会增加肿瘤的生长，而较高剂量的E2会明显降低肿瘤的生长。我们发现，E2处理可抑制这些细胞中的锚定非依赖性凋亡。同样，E2抑制了体内血管生成。有趣的是，E2的这些作用被雌激素受体β（ERβ）或Krüppel样锌指转录因子5（KLF5）的敲除所消除。此外，E2通过ERβ抑制了KLF5介导的转录，从而抑制了促凋亡的 FOXO1 和促血管生成的 PDGFA 的表达。此外，我们发现非激动性ER配体GS-1405通过ERβ-KLF5途径抑制 FOXO1 和 PDGF A表达并调节前列腺肿瘤的生长，而没有ERβ反式激活。因此，这些结果表明，E2通过调节经由ERβ的KLF5依赖性转录来双相调节前列腺肿瘤的形成，并为设计ER调节剂提供了新的策略，该调节剂将能够以最小的由于ER反式激活引起的不良反应调节前列腺癌的进展。

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