RRC ID 34844
Author 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.
Title The critical role of cyclin D2 in cell cycle progression and tumorigenicity of glioblastoma stem cells.
Journal Oncogene
Abstract 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.
Volume 32(33)
Pages 3840-5
Published 2013-8-15
DOI 10.1038/onc.2012.399
PII onc2012399
PMID 22964630
MeSH Animals Cell Cycle / physiology* Cell Line, Tumor Cyclin D2 / metabolism* Flow Cytometry Glioblastoma / metabolism* Glioblastoma / pathology Humans Immunoblotting Immunohistochemistry Mice Mice, Inbred BALB C Mice, Nude Neoplastic Stem Cells / metabolism* Neoplastic Stem Cells / pathology Oligonucleotide Array Sequence Analysis RNA Interference RNA, Small Interfering Reverse Transcriptase Polymerase Chain Reaction Transplantation, Heterologous
IF 6.634
Times Cited 31
DNA material pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) CS-RfA-CG (RDB04390) CSII-CMV-RfA-IRES2-Venus (RDB04388).