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Global analysis of CpG methylation reveals epigenetic control of the radiosensitivity in lung cancer cell lines

Oncogene volume 29, pages 4725–4731 (2010)Cite this article

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Abstract

Epigenetic regulation by CpG methylation has an important role in tumorigenesis as well as in the response to cancer therapy. To analyze the mechanism of epigenetic control of radiosensitivity, the CpG methylation profiles of radiosensitive H460 and radioresistant H1299 human non-small cell lung cancer (NSCLC) cell lines were analyzed using microarray profiling. These analyses revealed 1091 differentially methylated genes (DMG) (absolute difference of mean β-values, |Δβ¯|>0.5), including genes involved in cell adhesion, cell communication, signal transduction and transcriptional regulation. Among the 747 genes hypermethylated in radioresistant H1299 cells, CpG methylation of SERPINB5 and S100A6 in radioresistant H1299 cells was confirmed by methylation-specific PCR. Reverse transcriptase–PCR showed higher expression of these two genes in radiosensitive H460 cells compared with radioresistant H1299 cells. Downregulation of SERPINB5 or S100A6 by small interfering RNA in H460 cells increased the resistance of these cells to ionizing radiation. In contrast, promoter CpG sites of 344 genes, including CAT and BNC1, were hypomethylated in radioresistant H1299 cells. Suppression of CAT or BNC1 mRNA expression in H1299 cells also reduced the resistance of these cells to ionizing radiation. Thus, we identified DMGs by genome-wide CpG methylation profiling in two NSCLC cell lines with different responses to ionizing radiation, and our data indicated that these differences may be critical for epigenetic regulation of radiosensitivity in lung cancer cells.

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Acknowledgements

This research was supported by a grant from the Korea Science and Engineering Foundation (KOSEF), the Ministry of Education, Science and Technology, Korea (M20706000020-07M0600-02010 to WYP), and the Brain Korea21 (BK21) Program (WYP).

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  1. E-H Kim and A-K Park: These authors contributed equally to this work.

Authors and Affiliations

  1. Departments of Biomedical Sciences, Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea

    E-H Kim, A-K Park & W-Y Park

  2. Genomics Core Laboratory, Seoul National University College of Medicine, Seoul, Korea

    A-K Park & W-Y Park

  3. Division of Translational and Clinical Research I, Research Institute, National Cancer Center, Kyonggido, Seoul, Korea

    S M Dong

  4. Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Korea

    J-H Ahn

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  1. E-H Kim
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Correspondence to W-Y Park.

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Kim, EH., Park, AK., Dong, S. et al. Global analysis of CpG methylation reveals epigenetic control of the radiosensitivity in lung cancer cell lines. Oncogene 29, 4725–4731 (2010). https://doi.org/10.1038/onc.2010.223

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