• 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 >ERα as ligand-independent activator of CDH-1 regulates determination and maintenance of epithelial morphology in breast cancer cells
【24h】

ERα as ligand-independent activator of CDH-1 regulates determination and maintenance of epithelial morphology in breast cancer cells

机译：ERα作为CDH-1的配体非依赖性激活剂调节乳腺癌细胞上皮形态的确定和维持

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

Estrogen receptor α (ERα) and E-cadherin are primary markers of luminal epithelial breast cancer cells with E-cadherin being a main caretaker of the epithelial phenotype. E-cadherin repression is needed for cancer cells to acquire motile and invasive properties, and it is known that in ER-positive breast cancer cells, estrogen down-regulate E-cadherin gene transcription. We report here that ERα is bound to the E-cadherin promoter in both the presence and the complete absence of estrogen, suggesting an unexpected role for unliganded ERα in E-cadherin transcription. Indeed, our data reveal that activation by unliganded ERα and repression by estrogen-activated ERα require direct binding to a half-estrogen response element within the E-cadherin promoter and exchange from associated coactivators to corepressors. Therefore, these results suggest a pivotal role for unliganded ERα in controlling a fundamental caretaker of the epithelial phenotype in breast cancer cells. Here, we show that ERα-positive breast cancer T47D cells transduced with the sfRON kinase undergo a full epithelial-mesenchymal conversion and lose E-cadherin and ERα expression. Our data show that, although the E-cadherin gene becomes hy-permethylated and heterochromatic, kinase inhibitors can restore E-cadherin expression, together with an epithelial morphology in an ERα-dependent fashion. Similarly, transfection of ERα, in the absence of ligands, was sufficient to restore E-cadherin transcription in both sfRON-T47D and other ERα-, E-cadherin-negative cells. Therefore, our results suggest a novel role for the ERα that plays the dual role of ligand-independent activator and ligand-dependent repressor of E-cadherin in breast cancer cells.
机译：雌激素受体α（ERα）和E-cadherin是腔上皮乳腺癌细胞的主要标志物，E-cadherin是上皮表型的主要看护人。 E-cadherin抑制是癌细胞获得运动和侵袭特性所必需的，众所周知，在ER阳性乳腺癌细胞中，雌激素会下调E-cadherin基因的转录。我们在这里报告说，ERα在存在和完全不存在雌激素的情况下都与E-钙粘蛋白启动子结合，这暗示了在E-钙粘蛋白转录中未结合的ERα的意外作用。实际上，我们的数据表明，未配体的ERα的激活和雌激素激活的ERα的抑制需要与E-钙粘蛋白启动子内的半雌激素反应元件直接结合，并需要从相关的共激活子交换为共加压子。因此，这些结果表明未配体的ERα在控制乳腺癌细胞上皮表型的基本看守中起关键作用。在这里，我们显示，用sfRON激酶转导的ERα阳性乳腺癌T47D细胞经历了完整的上皮-间充质转化，并失去了E-钙黏着蛋白和ERα表达。我们的数据表明，尽管E-cadherin基因变得高甲基化和异色，但激酶抑制剂可以以ERα依赖性方式恢复E-cadherin的表达以及上皮形态。同样，在没有配体的情况下转染ERα足以恢复sfRON-T47D和其他ERα-，E-钙粘蛋白阴性细胞中的E-钙粘蛋白转录。因此，我们的结果表明，ERα在乳腺癌细胞中起着E-钙粘蛋白非配体依赖性激活剂和配体依赖性阻遏物双重作用。

著录项

  • 来源
  • 作者

    Maria Dafne Cardamone; Chiara Bardella; Arantxa Gutierrez; Luciano Di Croce; Michael G. Rosenfeld; Maria Flavia Di Renzo; Michele De Bortoli;

  • 作者单位

    Department of Medicine, Howard Hughes Medical Institute, University of California at San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0651 Department of Oncological Sciences, University of Torino, 10123 Turin, Italy Department of Center for Complex Systems in Molecular Biology and Medicine, University of Torino, 10123 Turin, Italy;

    Department of Oncological Sciences, University of Torino, 10123 Turin, Italy Laboratory of Cancer Genetics, Institute for Cancer Research and Treatment, University of Torino School of Medicine, 10060 Candiolo, Turin, Italy;

    Center for Genomic Regulation, Institucio Catalana de Recerca i Estudis Avancats, c/ Dr. Aiguader 88, 08003 Barcelona, Spain;

    Center for Genomic Regulation, Institucio Catalana de Recerca i Estudis Avancats, c/ Dr. Aiguader 88, 08003 Barcelona, Spain;

    Department of Medicine, Howard Hughes Medical Institute, University of California at San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0651;

    Department of Oncological Sciences, University of Torino, 10123 Turin, Italy Laboratory of Cancer Genetics, Institute for Cancer Research and Treatment, University of Torino School of Medicine, 10060 Candiolo, Turin, Italy;

    Department of Oncological Sciences, University of Torino, 10123 Turin, Italy Department of Center for Complex Systems in Molecular Biology and Medicine, University of Torino, 10123 Turin, Italy;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    E-cadherin; epithelial to mesenchymal transition; estrogen; invasion;

    机译：E-钙粘蛋白;上皮向间质转化;雌激素侵入;

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