Du Zhanhui, Jia Deyong, Liu Shangming, Wang Fuwu, Li Gang, Zhang Yanmin, Cao Xinmin, Ling Eng-Ang, Hao Aijun
Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong University School of Medicine, Jinan, China.
Glia. 2009 May;57(7):724-33. doi: 10.1002/glia.20800.
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.
越来越多的证据表明,癌细胞的自我更新能力对肿瘤发生至关重要;因此,研究这些细胞中自我更新调节基因的表达及作用至关重要。在此,我们报告称,Oct4作为胚胎干细胞中一种著名的自我更新调节因子,在人类胶质瘤及胶质瘤细胞系中高表达,且其表达水平随胶质瘤分级增加而升高。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,而在大鼠脑分化细胞中不表达。通过RNA干扰下调C6细胞中Oct4的表达与细胞增殖及集落形成减少相关。进一步分析表明,Oct4可上调Stat3的磷酸化以促进肿瘤细胞增殖。在C6细胞中过表达Oct4会增加巢蛋白的表达,但降低胶质纤维酸性蛋白的表达,提示Oct4可能抑制胶质瘤细胞的分化。我们的研究结果可能为肿瘤发生的干细胞理论提供进一步证据。相反,这些结果也可能意味着Oct4促成了胶质瘤中未分化细胞的存在。