The critical role of cyclin D2 in cell cycle progression and tumorigenicity of glioblastoma stem cells

被引：45
作者：
Koyama-Nasu, R. [1 ]
Nasu-Nishimura, Y. [1 ]
Todo, T. [2 ]
Ino, Y. [2 ]
Saito, N. [2 ]
Aburatani, H. [3 ]
Funato, K. [1 ]
Echizen, K. [1 ]
Sugano, H. [1 ]
Haruta, R. [1 ]
Matsui, M. [1 ]
Takahashi, R. [1 ]
Manabe, E. [1 ]
Oda, T. [1 ]
Akiyama, T. [1 ]
机构：
[1] Univ Tokyo, Inst Mol & Cellular Biosci, Lab Mol & Genet Informat, Bunkyo Ku, Tokyo 1100032, Japan
[2] Tokyo Univ Hosp, Dept Neurosurg, Bunkyo Ku, Tokyo 113, Japan
[3] Univ Tokyo, Genome Sci Div, Res Ctr Adv Sci & Technol, Meguro Ku, Tokyo 1100032, Japan
来源：
ONCOGENE | 2013年 / 32卷 / 33期
关键词：
cancer stem cells; cell cycle; cyclin D2; glioblastoma; CANCER; PROLIFERATION; PATHWAYS; GLIOMAS; ORIGIN; TUMORS; BRAIN; LINES;
D O I：
10.1038/onc.2012.399
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
引用
收藏
页码：3840 / 3845
页数：6
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