J Cancer 2016; 7(3):344-352. doi:10.7150/jca.13396 This issue

Research Paper

Proton Beams Inhibit Proliferation of Breast Cancer Cells by Altering DNA Methylation Status

Byungtak Kim1, Hansol Bae1, Hyunkyung Lee1, Seungyeon Lee1, Jeong Chan Park2, Kye Ryung Kim2, Sun Jung Kim1,✉

1. Department of Life Science, Dongguk University-Seoul, Goyang, Korea;
2. Korea Multi-purpose Accelerator Complex, Korea Atomic Energy Research Institute, Gyeongju, Korea

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Kim B, Bae H, Lee H, Lee S, Park JC, Kim KR, Kim SJ. Proton Beams Inhibit Proliferation of Breast Cancer Cells by Altering DNA Methylation Status. J Cancer 2016; 7(3):344-352. doi:10.7150/jca.13396. Available from https://www.jcancer.org/v07p0344.htm

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Proton beam therapy has been gaining popularity in the management of a wide spectrum of cancers. However, little is known about the effect of proton beams on epigenetic alterations. In this study, the effects of proton beams on DNA methylation were evaluated in the breast cell lines MCF-10A and MCF-7. Pyrosequencing analysis of the long interspersed element 1 (LINE1) gene indicated that a few specific CpG sites were induced to be hypermethylated by proton beam treatment from 64.5 to 76.5% and from 57.7 to 60.0% (p < 0.05) in MCF-10A and MCF-7, respectively. Genome-wide methylation analysis identified “Developmental Disorder, Hereditary Disorder, Metabolic Disease” as the top network in the MCF-7 cell line. The proliferation rate significantly decreased in proton beam-treated cells, as judged by colony formation and cell proliferation assay. Upon treatment with the proton beam, expression of selected genes (MDH2, STYXL1, CPE, FAM91A1, and GPR37) was significantly changed in accordance with the changes of methylation level. Taken together, the findings demonstrate that proton beam-induced physiological changes of cancer cells via methylation modification assists in establishing the epigenetic basis of proton beam therapy for cancer.

Keywords: Alu, breast cancer, epigenetics, LINE1, methylation, proton beam