Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Kim B

PROVIDER: S-EPMC4747889 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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

Kim Byungtak B Bae Hansol H Lee Hyunkyung H Lee Seungyeon S Park Jeong Chan JC Kim Kye Ryung KR Kim Sun Jung SJ

Journal of Cancer 20160110 3

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 fr ...[more]

PMID: 26918048

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Project description:We examined whether differences in tumor DNA methylation were associated with more aggressive hormone receptor-negative breast cancer in an ethnically diverse group of patients in the Breast Cancer Care in Chicago (BCCC) study and using data from The Cancer Genome Atlas (TCGA).DNA was extracted from formalin-fixed, paraffin-embedded samples on 75 patients (21 White, 31 African-American, and 23 Hispanic) (training dataset) enrolled in the BCCC. Hormone receptor status was defined as negative if tumors were negative for both estrogen and progesterone (ER/PR) receptors (N?=?22/75). DNA methylation was analyzed at 1505 CpG sites within 807 gene promoters using the Illumina GoldenGate assay. Differential DNA methylation as a predictor of hormone receptor status was tested while controlling for false discovery rate and assigned to the gene closest to the respective CpG site. Next, those genes that predicted ER/PR status were validated using TCGA data with respect to DNA methylation (validation dataset), and correlations between CpG methylation and gene expression were examined. In the training dataset, 5.7 % of promoter mean methylation values (46/807) were associated with receptor status at P?<?0.05; for 88 % of these (38/46), hypermethylation was associated with receptor-positive disease. Hypermethylation for FZD9, MME, BCAP31, HDAC9, PAX6, SCGB3A1, PDGFRA, IGFBP3, and PTGS2 genes most strongly predicted receptor-positive disease. Twenty-one of 24 predictor genes from the training dataset were confirmed in the validation dataset. The level of DNA methylation at 19 out 22 genes, for which gene expression data were available, was associated with gene activity.Higher levels of promoter methylation strongly correlate with hormone receptor positive status of breast tumors. For most of the genes identified in our training dataset as ER/PR receptor status predictors, DNA methylation correlated with stable gene expression level. The predictors performed well when evaluated on independent set of samples, with different racioethnic distribution, thus providing evidence that this set of DNA methylation biomarkers will likely generalize to prospective patient samples.

Dataset Information

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

Publications

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

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