Brain cancer stem-like cell genesis from p53-deficient mouse astrocytes by oncogenic Ras
Brain cancer stem-like cell genesis from p53-deficient mouse astrocytes by oncogenic Ras
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DOI：
10.1016/j.bbrc.2007.11.005
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发表时间：
2008-01-18
影响因子：
3.1
通讯作者：
Kim, Hyunggee
中科院分区：
文献类型：
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作者：
Lee, Joong-Seob;Gil, Jung-Eun;Kim, Hyunggee
在这里，我们发现 H-ras(v12) 导致 p53 敲除的小鼠星形胶质细胞 (p53-/- 星形胶质细胞) 转化为脑癌干细胞样细胞。 H-ras(v12) 触发 p53-/- 星形胶质细胞表达巢蛋白和 Cd133，它们在正常和癌症神经干细胞中表达。 H-ras(V12) 还在神经干细胞培养条件下诱导单细胞源性神经球的形成。此外，H-ras(_)(V12)过表达p53-/-星形胶质细胞(p53-/-ast-H-ras(v12))具有体外自我更新能力，并且在体外和体内均异常分化为Tuj 1阳性神经元。在多种Ras介导的经典信号通路中，我们证明MEK/ERK信号通路负责P53缺陷的星形胶质细胞中神经球的形成，而PI3K/AKT信号通路参与这些细胞的致癌转化。这些发现表明，Ras 信号通路的激活通过改变细胞命运和转变细胞特性，促进 p53 缺陷的小鼠星形胶质细胞生成脑癌干细胞样细胞。 (c) 2007 Elsevier Inc. 保留所有权利。
Here, we show that H-ras(v12) causes the p53-knockout mouse astrocytes (p53-/- astrocytes) to be transformed into brain cancer stem-like cells. H-ras(v12) triggers the p53-/- astrocytes to express a Nestin and a Cd133, which are expressed in normal and cancer neural stem cells. H-ras(V12) also induces the formation of a single cell-derived neurosphere under neural stem cell culture conditions. Furthermore, H-ras(_)(V12)overexpressing p53-/- astrocytes (p53-/-ast-H-ras(v12)) possess an in vitro self-renewal capacity, and are aberrantly differentiated into Tuj 1-positve neurons both in vitro and in vivo. Amongst a variety of Ras-mediated canonical signaling pathways, we demonstrated that the MEK/ERK signaling pathway is responsible for neurosphere formation in P53-deficient astrocytes, whereas the PI3K/AKT signaling pathway is involved in oncogenic transformation in these cells. These findings suggest that the activation of Ras signaling pathways promotes the generation of brain cancer stem-like cells from p53-deficient mouse astrocytes by changing cell fate and transforming cell properties. (c) 2007 Elsevier Inc. All rights reserved.