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

• Published in: Oncogene Vol. 32; no. 33; pp. 3840 - 3845
• Main Authors: Koyama-Nasu, R, Nasu-Nishimura, Y, Todo, T, Ino, Y, Saito, N, Aburatani, H, Funato, K, Echizen, K, Sugano, H, Haruta, R, Matsui, M, Takahashi, R, Manabe, E, Oda, T, Akiyama, T
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.08.2013; Nature Publishing Group
• Subjects: Animals; Apoptosis; Brain cancer; Brain tumors; Cell Biology; Cell cycle; Cell Cycle - physiology; Cell differentiation; Cell Line, Tumor; Cyclin D proteins; Cyclin D2; Cyclin D2 - metabolism; Development and progression; Flow Cytometry; Gene expression; Genetic aspects; Glioblastoma; Glioblastoma - metabolism; Glioblastoma - pathology; Glioblastoma cells; Glioblastoma multiforme; Growth rate; Human Genetics; Humans; Immunoblotting; Immunohistochemistry; Internal Medicine; Medicine; Medicine & Public Health; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular modelling; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Oligonucleotide Array Sequence Analysis; Oncology; original-article; Pathogenesis; Physiological aspects; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; RNA, Small Interfering; RNA-mediated interference; Stem cell transplantation; Stem cells; Transplantation, Heterologous; Tumorigenicity; Xenografts; Japan; cyclin D2; glioblastoma; cancer stem cells; cell cycle
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2012.399

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.