• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国政府科技报告 >Prolactin Receptor Coupling to Jak-Stat Pathways in Breast Cancer
【24h】

Prolactin Receptor Coupling to Jak-Stat Pathways in Breast Cancer

机译：催乳素受体与乳腺癌Jak-stat通路偶联

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

摘要

Prolactin receptors (PRLR) have been considered selective activators of tyrosine kinase Jak2 but not Jak1, Jak3 or Tyk2. We now report marked PRL-induced tyrosine phosphorylation of Jak1, in addition to Jak2, in a series of human breast cancer cell lines, including T47D, MCF7, and SKBR3. In contrast, PRL did not activate Jak1 in immortalized, noncancerous breast epithelial lines HC11, MCF10A, ME16C, and HBL-100, or in CWR22Rv1 prostate cancer cells or MDA-MB-231 breast cancer cells. However, introduction of exogenous PRLR into MCF10A, ME16C, or MDA-MB-231 cells reconstituted both PRL-Jak1 and PRL-Jak2 signals. PRL activated Jak1 through a Jak2-dependent mechanism in T47D cells, based on disruption of PRL activation of Jak1 following Jak2 suppression by 1) lentiviral delivery of Jak2 shRNA, 2) adenoviral delivery of dominant-negative Jak2, and 3) AG490 pharmacological inhibition. Finally, suppression of Jak1 by lentiviral delivery of Jak1 shRNA blocked PRL activation of ERK and Stat3, and suppressed PRL activation of Jak2, Stat5a, Stat5b, and Akt, as well as tyrosine phosphorylation of PRLR. The data suggest that PRL activation of Jak1 represents a novel, Jak2-dependent mechanism that may serve as a regulatory switch leading to PRL activation of ERK and Stat3 pathways, while also serving to enhance PRL-induced Stat5a/b and Akt signaling.

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