...
  • 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 >STAT3- and DNA methyltransferase 1-mediated epigenetic silencing of SHP-1 tyrosine phosphatase tumor suppressor gene in malignant T lymphocytes
【24h】

STAT3- and DNA methyltransferase 1-mediated epigenetic silencing of SHP-1 tyrosine phosphatase tumor suppressor gene in malignant T lymphocytes

机译：STAT3和DNA甲基转移酶1介导的SHP-1酪氨酸磷酸酶肿瘤抑制基因在恶性T淋巴细胞中的表观遗传沉默

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

Expression of SHP-1 phosphatase, a key negative regulator of cell signaling, is lost in T cell lymphomas and other malignancies due to DNA methylation of the SHP-1 promoter by a currently undefined mechanism. We demonstrate that malignant T cells express DNA methyltransferase (DNMT) 1 and that constantly activated signal transducer and activator of transcription (STAT) 3 is capable of binding in vitro to DNA oligonucleotides corresponding to four STAT3 SIE/GAS binding sites identified in the SHP-1 promoter. STAT3, DNMT1, and histone deacetylase 1 form complexes and bind to the SHP-1 promoter in vivo. Treatment with pharmacologic grade DNMT1 anti-sense oligonucleotides and STAT3 small-interfering RNA induces in the malignant T cells DNA demethylation and expression of SHP-1 gene. These data indicate that STAT3 may, in part, transform cells by inducing epigenetic silencing of SHP-1 in cooperation with DNMT1 and, apparently, histone deacetylase 1. Reversal of such gene silencing represents an attractive aim for novel anticancer therapies.
机译：由于目前尚未确定的机制，由于SHP-1启动子的DNA甲基化，T细胞淋巴瘤和其他恶性肿瘤中SHP-1磷酸酶（一种重要的细胞信号负调节剂）的表达丢失。我们证明恶性T细胞表达DNA甲基转移酶（DNMT）1，并且不断激活的信号转导子和转录激活子（STAT）3能够在体外与DNA寡核苷酸结合，该寡核苷酸对应于SHP-中鉴定的四个STAT3 SIE / GAS结合位点。 1个启动子。 STAT3，DNMT1和组蛋白脱乙酰基酶1在体内形成复合物并与SHP-1启动子结合。用药理学级DNMT1反义寡核苷酸和STAT3小干扰RNA处理可诱导恶性T细胞DNA脱甲基和SHP-1基因表达。这些数据表明，STAT3可以通过与DNMT1以及显然与组蛋白脱乙酰基酶1协同诱导SHP-1的表观遗传沉默来部分转化细胞。这种基因沉默的逆转代表了新型抗癌治疗的诱人目标。

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