Abstract
Abstract Epigenetic regulation is one of the most important mechanisms for the development and the progression of human cancers. To understand the epigenetic control of differential sensitivity to radiotherapy, we investigated the DNA CpG methylation profiles of normal lung epithelial cells and lung cancer cell lines using DNA microarray. Among 27K CpG probes in Illumina BeadChip, we found CpG sites of 1091 genes were differentially methylated in radiosensitive H460 and radioresistant H1299 cell lines against normal lung cells. Among the hypermethylated genes in H1299 cells, promoter CpG methylation and mRNA expression of SERPINB5 and S100A6 were validated by methylation-specific PCR and quantitative RT-PCR, respectively. When we suppressed the expression of these two genes using siRNA in H460 cells, the survival fraction of H460 cells were increased upon ionizing radiation. Promoter CpG sites of CAT and BNC1 were hypomethylated in radioresistant H1299 cells and the introduction of siRNA against CAT or BNC1 in H1299 cells could reduce the resistance to ionizing radiation. Here we report the differentially methylated genes by genome-wide CpG methylation profiling in two lung cancer cell lines, which might prove the epigenetic regulation of radiosensitivity in lung cancer cells. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B7.
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