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

Oncogene volume 32, pages 3840–3845 (2013)Cite this article

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.

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Acknowledgements

This work was supported by Research Program of Innovative Cell Biology by Innovative Technology (Integrated Systems Analysis of Cellular Oncogenic Signaling Networks), Grants-in-Aid for Scientific Research on Innovative Areas (Integrative Research on Cancer Microenvironment Network), Takeda Science Foundation and in part by Global COE Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms), MEXT, Japan.

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Author notes

  1. R Koyama-Nasu and Y Nasu-Nishimura: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan,

    R Koyama-Nasu, Y Nasu-Nishimura, K Funato, K Echizen, H Sugano, R Haruta, M Matsui, R Takahashi, E Manabe, T Oda & T Akiyama

  2. Department of Neurosurgery, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan,

    T Todo, Y Ino & N Saito

  3. Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Meguro-ku, Tokyo, Japan

    H Aburatani

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  1. R Koyama-Nasu
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  2. Y Nasu-Nishimura
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  5. N Saito
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  7. K Funato
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  8. K Echizen
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  10. R Haruta
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  11. M Matsui
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  12. R Takahashi
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  13. E Manabe
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  15. T Akiyama
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Corresponding author

Correspondence to T Akiyama.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on the Oncogene website

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Koyama-Nasu, R., Nasu-Nishimura, Y., Todo, T. et al. The critical role of cyclin D2 in cell cycle progression and tumorigenicity of glioblastoma stem cells. Oncogene 32, 3840–3845 (2013). https://doi.org/10.1038/onc.2012.399

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  • DOI: https://doi.org/10.1038/onc.2012.399

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