Oct4 is Expressed in Human Gliomas and Promotes Colony Formation in Glioma Cells
Oct4 is Expressed in Human Gliomas and Promotes Colony Formation in Glioma Cells
复制标题
Oct4 在人类神经胶质瘤中表达并促进神经胶质瘤细胞集落形成
DOI：
10.1002/glia.20800
复制
发表时间：
2009-05-01
期刊：
影响因子：
6.2
通讯作者：
Hao, Aijun
中科院分区：
文献类型：
--
作者：
Du, Zhanhui;Jia, Deyong;Hao, Aijun
越来越多的证据表明癌细胞的自我更新能力对于癌变至关重要。因此，检查这些细胞中自我更新调节基因的表达和参与至关重要。在这里，我们报道了Oct4，一种著名的胚胎干细胞自我更新调节因子，在人神经胶质瘤和神经胶质瘤细胞系中高表达，并且表达水平随着神经胶质瘤级别的增加而增加。在体外细胞培养中，Oct4仅在大鼠C6胶质瘤细胞和大鼠神经干细胞中表达，但在大鼠脑分化细胞中不表达。 C6 细胞中 RNA 干扰下调 Oct4 表达与细胞增殖和集落形成减少有关。进一步分析发现Oct4可以上调Stat3的磷酸化从而促进肿瘤细胞增殖。 C6细胞中Oct4的过度表达增加了巢蛋白的表达，但降低了GFAP的表达，表明Oct4可能抑制胶质瘤细胞的分化。我们的研究结果可能为干细胞致癌理论提供进一步的证据。相比之下，结果也可能意味着 Oct4 有助于神经胶质瘤中未分化细胞的存在。 (C) 2008 Wiley-Liss, Inc.
There is increasing evidence that self-renewal capacity of cancer cells is critical for carcinogenesis; hence, it is vital to examine the expression and involvement of self-renewal regulatory genes in these cells. Here, we reported that Oct4, a well-known regulator of self-renewal in embryonic stem cells, was highly expressed in human gliomas and glioma cell lines, and the expression levels were increased in parallel with increasing glioma grades. In in vitro cell cultures, Oct4 was only expressed in rat C6 glioma cells and rat neural stem cells but not in rat brain differentiated cells. Downregulation of Oct4 expression by RNA interference in C6 cells was associated with reduced cell proliferation and colony formation. Further analysis revealed that Oct4 could upregulate phosphorylation of Stat3 to promote tumor cell proliferation. Overexpression of Oct4 in C6 cells increased the expression of nestin but decreased the expression of GFAP suggesting that Oct4 might inhibit the differentiation of glioma cells. Our findings may provide further evidence for the stem cell theory of carcinogenesis. In contrast, the results might also imply that Oct4 contributes to the existence of undifferentiated cells in gliomas. (C) 2008 Wiley-Liss, Inc.