title: The critical role of cyclin D2 in cell cycle progression and tumorigenicity of glioblastoma stem cells.
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.
authors.affiliation: Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Koyama-Nasu
authors.forename: Y
authors.initials: Y
authors.lastname: Nasu-Nishimura
authors.forename: T
authors.initials: T
authors.lastname: Todo
authors.forename: Y
authors.initials: Y
authors.lastname: Ino
authors.forename: N
authors.initials: N
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Aburatani
authors.forename: K
authors.initials: K
authors.lastname: Funato
authors.forename: K
authors.initials: K
authors.lastname: Echizen
authors.forename: H
authors.initials: H
authors.lastname: Sugano
authors.forename: R
authors.initials: R
authors.lastname: Haruta
authors.forename: M
authors.initials: M
authors.lastname: Matsui
authors.forename: R
authors.initials: R
authors.lastname: Takahashi
authors.forename: E
authors.initials: E
authors.lastname: Manabe
authors.forename: T
authors.initials: T
authors.lastname: Oda
authors.forename: T
authors.initials: T
authors.lastname: Akiyama
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D056742:Cyclin D2 / Q000378:metabolism*; D005434:Flow Cytometry; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: C080336:CCND2 protein, human; D056742:Cyclin D2; D034741:RNA, Small Interfering