Functional analysis of HOXD9 in human gliomas and glioma cancer stem cells

Molecular Cancer

Research

Takeshi Kawase¹  Kazunari Yoshida¹  Yutaka Kawakami²  Aya Misawa²  Hideyuki Saya³  Hideyuki Okano⁴  Yumi Matsuzaki⁴  Yohei Ohashi⁵  Masanao Tabuse⁶  Raita Fukaya⁶  Masahiro Toda⁶  Shigeki Ohta⁷  Hérve Chneiweiss⁸  Cécile Thirant⁸ 

[1] Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, 160-8582, Shinjuku-ku, Tokyo, Japan;Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, 160-8582, Shinjuku-ku, Tokyo, Japan;Division of Gene Regulation, Institute for Advanced Medical Research of Keio University School of Medicine, 35 Shinanomachi, 160-8582, Shinjuku-ku, Tokyo, Japan;Division of Physiology, Keio University School of Medicine, 35 Shinanomachi, 160-8582, Shinjuku-ku, Tokyo, Japan;Neuroimmunology Research Group, Keio University School of Medicine, 35 Shinanomachi, 160-8582, Shinjuku-ku, Tokyo, Japan;Neuroimmunology Research Group, Keio University School of Medicine, 35 Shinanomachi, 160-8582, Shinjuku-ku, Tokyo, Japan;Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, 160-8582, Shinjuku-ku, Tokyo, Japan;Neuroimmunology Research Group, Keio University School of Medicine, 35 Shinanomachi, 160-8582, Shinjuku-ku, Tokyo, Japan;Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, 160-8582, Shinjuku-ku, Tokyo, Japan;Team Glial Plasticity Inserm UMR 894, University Paris Descartes, 75014, Paris, France;

关键词: Glioma Cell;    Side Population;    Side Population Cell;    Restriction Landmark Genomic Scanning;    HOXD9 Gene;   

DOI  :  10.1186/1476-4598-10-60

 received in 2010-12-03, accepted in 2011-05-22,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundHOX genes encode a family of homeodomain-containing transcription factors involved in the determination of cell fate and identity during embryonic development. They also behave as oncogenes in some malignancies.ResultsIn this study, we found high expression of the HOXD9 gene transcript in glioma cell lines and human glioma tissues by quantitative real-time PCR. Using immunohistochemistry, we observed HOXD9 protein expression in human brain tumor tissues, including astrocytomas and glioblastomas. To investigate the role of HOXD9 in gliomas, we silenced its expression in the glioma cell line U87 using HOXD9-specific siRNA, and observed decreased cell proliferation, cell cycle arrest, and induction of apoptosis. It was suggested that HOXD9 contributes to both cell proliferation and/or cell survival. The HOXD9 gene was highly expressed in a side population (SP) of SK-MG-1 cells that was previously identified as an enriched-cell fraction of glioma cancer stem-like cells. HOXD9 siRNA treatment of SK-MG-1 SP cells resulted in reduced cell proliferation. Finally, we cultured human glioma cancer stem cells (GCSCs) from patient specimens found with high expression of HOXD9 in GCSCs compared with normal astrocyte cells and neural stem/progenitor cells (NSPCs).ConclusionsOur results suggest that HOXD9 may be a novel marker of GCSCs and cell proliferation and/or survival factor in gliomas and glioma cancer stem-like cells, and a potential therapeutic target.

【 授权许可】

Unknown   
© Tabuse et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.