Histone H2AX sensitizes glioma cells to genotoxic stimuli by recruiting DNA double-strand break repair proteins

Momota,Hiroyuki; Ichimiya,Shingo; Kondo,Nobuhiko; Kikuchi,Tomoki; Torigoe,Toshihiko; Yamaki,Toshiaki; Houkin,Kiyohiro; Sato,Noriyuki

doi:10.3892/ijo.23.2.311

August 2003 Volume 23 Issue 2

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August 2003 Volume 23 Issue 2

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Article

Histone H2AX sensitizes glioma cells to genotoxic stimuli by recruiting DNA double-strand break repair proteins

Authors:
- Hiroyuki Momota
- Shingo Ichimiya
- Nobuhiko Kondo
- Tomoki Kikuchi
- Toshihiko Torigoe
- Toshiaki Yamaki
- Kiyohiro Houkin
- Noriyuki Sato
View Affiliations / Copyright

Affiliations: Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan
Pages: 311-315
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Published online on: August 1, 2003

https://doi.org/10.3892/ijo.23.2.311
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Abstract

Glioblastoma is a life-threatening tumor in the human brain despite the fact that radio-chemotherapy inducing DNA damage has been improved in the last decade. Various studies focusing on the enhancement of the susceptibility of glioblastoma cells to DNA damage have been reported, which are aimed at more efficient treatment for the tumor. In this study, we show that radioresistant T98G glioblastoma cells can develop sensitivity to DNA damage induced by irradiation and etoposide as a result of the introduction of a DNA repair-associated histone, H2AX. Interestingly, when H2AX-transformed T98G cells were irradiated, Brca1 and Nbs1 were readily recruited in DNA double-strand break (DSB) foci and showed the G2/M-phase arrest of the cell cycle. Moreover, up-regulation of Brca1 was observed in H2AX-T98G cells after exposure to irradiation. Together with the evidence that H2AX transfection does not affect growth activities of non-tumor cells under genotoxic stimuli, this suggests that H2AX gene transfer would provide a new modality for radio-chemotherapy for glioblastomas, probably through overcoming the instability of the genome, and that Brca1 and Nbs1 might be crucial in this methodology.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Histone H2AX sensitizes glioma cells to genotoxic stimuli by recruiting DNA double-strand break repair proteins

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