Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Oncogene. 2013 Aug 15;32(33):3840-5. doi: 10.1038/onc.2012.399. Epub 2012 Sep 10.
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.
癌症干细胞被认为是肿瘤发生和发展的根源。目前，许多针对人脑肿瘤的研究都集中在神经胶质瘤干细胞（GSCs）的干细胞样特性上。然而，人们对区分 GSCs 和分化的神经胶质瘤细胞的细胞周期调控的分子机制知之甚少。在这里，我们表明细胞周期蛋白 D2 是在 GSCs 中主要表达的细胞周期蛋白，通过 RNA 干扰抑制其表达会导致体外 G1 期停滞和体内免疫缺陷小鼠移植的 GSCs 生长迟缓。我们还证明，与癌症干细胞标记物 CD133 观察到的情况类似，在血清诱导分化时，cyclin D2 的表达受到抑制。总之，我们的研究结果表明，cyclin D2 在 GSCs 的细胞周期进程和致瘤性中起着关键作用。
