The critical role of cyclin D2 in cell cycle progression and tumorigenicity of glioblastoma stem cells
The critical role of cyclin D2 in cell cycle progression and tumorigenicity of glioblastoma stem cells
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DOI：
10.1038/onc.2012.399
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发表时间：
2013-08-15
期刊：
影响因子：
8
通讯作者：
Akiyama, T.
中科院分区：
文献类型：
--
作者：
Koyama-Nasu, R.;Nasu-Nishimura, Y.;Akiyama, T.
肿瘤干细胞被认为与肿瘤的发生和发展有关。目前对人脑肿瘤的研究主要集中在胶质母细胞瘤干细胞(GSCs)的干细胞特性上。然而，对区分GSCs和分化的胶质母细胞瘤细胞的细胞周期调控的分子机制知之甚少。在这里，我们发现细胞周期蛋白D2是一种主要在GSCs中表达的细胞周期蛋白，通过RNA干扰抑制其表达会导致GSCs在体外的G1期停滞和体内移植到免疫缺陷小鼠体内的GSCs生长迟缓。我们还证明，在血清诱导分化时，细胞周期蛋白D2的表达被抑制，类似于观察到的癌症干细胞标记CD133的表达。综上所述，我们的结果表明，细胞周期蛋白D2在细胞周期进程和GSCs的致瘤性中起着关键作用。
Cancer stem cells are believed to be responsible for tumor initiation and development. Much current research on human brain tumors is focused on the stem-like properties of glioblastoma stem cells (GSCs). However, little is known about the molecular mechanisms of cell cycle regulation that discriminate between GSCs and differentiated glioblastoma cells. Here we show that cyclin D2 is the cyclin that is predominantly expressed in GSCs and suppression of its expression by RNA interference causes G1 arrest in vitro and growth retardation of GSCs xenografted into immunocompromised mice in vivo. We also demonstrate that the expression of cyclin D2 is suppressed upon serum-induced differentiation similar to what was observed for the cancer stem cell marker CD133. Taken together, our results demonstrate that cyclin D2 has a critical role in cell cycle progression and the tumorigenicity of GSCs.