...
首页> 外文期刊>Oncogene >The zinc-finger transcription factor GLI2 antagonizes contact inhibition and differentiation of human epidermal cells
【24h】

The zinc-finger transcription factor GLI2 antagonizes contact inhibition and differentiation of human epidermal cells

机译:锌指转录因子GLI2拮抗人类表皮细胞的接触抑制和分化

获取原文
           

摘要

In stratified epidermis, activation of the Hh/Gli signal transduction pathway has been implicated in the control of cell proliferation and tumorigenesis. The zinc-finger transcription factor Gli2 has been identified as critical mediator of the Hh signal at the distal end of the pathway, but the molecular mechanisms by which Gli2 regulates cell proliferation or induces epidermal malignancies such as basal cell carcinoma are still unclear. Here, we provide evidence for a role of human GLI2 in antagonizing contact inhibition and epidermal differentiation. We show by gene expression profiling that activation of the GLI2 oncogene in human keratinocytes activates the transcription of a number of genes involved in cell cycle progression such as E2F1, CCND1, CDC2 and CDC45L, while it represses genes associated with epidermal differentiation. Analysis of the proliferative effect of GLI2 revealed that GLI2 is able to induce G1–Sphase progression in contact-inhibited keratinocytes. Detailed time-course experiments identified E2F1 as early transcriptional target of GLI2. Further, we show that GLI2 expression in human keratinocytes results in a marked downregulation of epidermal differentiation markers. The data suggest a role for GLI2 in Hh-induced epidermal neoplasia by opposing epithelial cell cycle arrest signals and epidermal differentiation.
机译:在分层表皮中,Hh / Gli信号转导途径的激活与细胞增殖和肿瘤发生的控制有关。锌指转录因子Gli2已被确定为该通路远端Hh信号的关键介体,但尚不清楚Gli2调节细胞增殖或诱导表皮恶性肿瘤(如基底细胞癌)的分子机制。在这里,我们提供了人类GLI2在拮抗接触抑制和表皮分化中的作用的证据。我们通过基因表达谱显示,人角质形成细胞中GLI2癌基因的激活可以激活许多参与细胞周期进程的基因的转录,例如E2F1,CCND1,CDC2和CDC45L,同时它抑制与表皮分化相关的基因。对GLI2增殖作用的分析表明,GLI2能够在接触抑制的角质形成细胞中诱导G1期进展。详细的时程实验确定E2F1为GLI2的早期转录靶标。此外,我们表明,人类角​​质形成细胞中的GLI2表达导致表皮分化标记物的显着下调。数据表明,GLI2在Hh诱导的表皮瘤形成中的作用是通过对抗上皮细胞周期停滞信号和表皮分化。

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