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

E. H. Kim, A. K. Park, S. M. Dong, J. H. Ahn, W. Y. Park

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

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.

Original languageEnglish
Pages (from-to)4725-4731
Number of pages7
JournalOncogene
Volume29
Issue number33
DOIs
StatePublished - 19 Aug 2010

Keywords

  • CpG methylation
  • ionizing radiation
  • microarray
  • radiosensitivity

Fingerprint

Dive into the research topics of 'Global analysis of CpG methylation reveals epigenetic control of the radiosensitivity in lung cancer cell lines'. Together they form a unique fingerprint.

Cite this