@misc{oai:repo.qst.go.jp:00070413,
 author = {Ishikawa, Kenichi and Fujita, Mayumi and Iizuka, Daisuke and Imai, Takashi and 石川 顕一 and 藤田 真由美 and 飯塚 大輔 and 今井 高志},
 month = {Mar},
 note = {Identifying and characterizing regulators of cancer metastasis is important for cancer therapy. We recently investigated the induction of cellular invasiveness after X-ray irradiation in the MIAPaCa-2 cell line derived from human pancreatic cancer. Transcription levels of metalloproteinase 2 (MMP2) were increased drastically after X-ray irradiation. MMPs have been implicated in increased invasive and metastatic potential of tumors, possibly via interactions with the extracellular matrix. This radiation-induced invasiveness was different in irradiated PANC-1 cells that are also derived from human pancreatic cancer. Furthermore, this response in MIAPaCa-2 cells irradiated by X-ray was different from that in the same cells irradiated by carbon ion beam.
DNA methylation is an epigenetic modification that occurs in mammals to ensure the proper regulation of gene expression in response to environmental stimuli and stable gene silencing. However, the source of variation in DNA methylation itself remains poorly understood. We hypothesized that tumor cells can change their invasiveness after irradiation via epigenetic processes such as DNA methylation. 
In this study, we measured DNA methylation at 27,578 CpG islands in MIAPaCa-2 and PANC-1 at 48 h after irradiation with either X-rays at 4 Gy or a carbon ion beam at 2 Gy using the HumanMethylation27 BeadChip. Many CpG islands in MIAPaCa-2 showed higher DNA methylation status compared with those in PANC-1 cells. Some CpG islands changed DNA methylation status after irradiation, but the MMP2 locus exhibited an almost completely methylated status both before and after X-ray irradiation in MIAPaCa-2 cells. It is possible that the MMP2 locus designed for the BeadChip probes used here represent discrete regions of the MMP2 locus recognized by X-ray-responsive transcription factors in MIAPaCa-2. We have now designed an experiment to measure DNA methylation status at high density using next generation sequencing technology. A methylated DNA enriched sample and an unmethylated DNA enriched sample are being analyzing in ongoing work to compare the methylation status of the radiation-responsive genes including MMP2., 1st RIRBM International Symposium},
 title = {Epigenetic regulation of tumor cell invasiveness induced by irradiation},
 year = {2011}
}