Notch signaling enhances nestin expression in gliomas
Notch signaling enhances nestin expression in gliomas
复制标题
DOI：
10.1593/neo.06526
复制
发表时间：
2006-12-01
期刊：
影响因子：
4.8
通讯作者：
Holland, Eric C.
中科院分区：
文献类型：
--
作者：
Shih, Alan H.;Holland, Eric C.
最近的研究表明，Notch信号在脑肿瘤和干细胞中是活跃的，并且干细胞或具有祖细胞特征的细胞参与脑肿瘤的形成。这些干细胞通过几种标记物的表达来标记，包括巢蛋白，一种中间丝蛋白。我们研究了Notch信号通路如何影响nestin在脑肿瘤中的表达。我们发现Notch受体和配体在体外和人类胶质母细胞瘤（最高级别的恶性胶质瘤）样本中表达。在培养中，Notch活性激活巢蛋白启动子。在Kras诱导的多形性胶质母细胞瘤小鼠模型中，Notch通路也被激活，翻译调节在Notch表达中起作用。Notch和Kras在野生型巢蛋白表达细胞中的联合激活导致它们在室下区扩张，并保持增殖和巢蛋白表达。然而，单独激活Notch无法诱导这种细胞扩增。这些数据表明Notch可能在神经胶质瘤细胞的干细胞样特性中起着重要作用。
Recent findings suggest that Notch signaling is active in brain tumors and stem cells, and that stem cells or cells with progenitor characteristics contribute to brain tumor formation. These stem cells are marked by expression of several markers, including nestin, an intermediate filament protein. We have studied how the Notch signaling pathway affects nestin expression in brain tumors. We find that Notch receptors and ligands are expressed in vitro and in human samples of glioblastomas, the highest grade of malignant gliomas. In culture, Notch activity activates the nestin promoter. Activation of the Notch pathway also occurs in a glioblastoma multiforme mouse model induced by Kras, with translational regulation playing a role in Notch expression. Combined activation of Notch and Kras in wild-type nestin-expressing cells leads to their expansion within the subventricular zone and retention of proliferation and nestin expression. However, activation of Notch alone is unable to induce this cellular expansion. These data suggest that Notch may have a contributing role in the stem-like character of glioma cells.