Infrequently methylated event at sites −362 to −142 in the promoter of TGFβR1 gene in non-small cell lung cancer

Abstract

Many malignant tumor cells, including non-small cell lung cancer (NSCLC) cells, are frequently resistant to transforming growth factor beta (TGF-beta)-mediated signal transduction. This refractory response might be due to reduced/loss expression of the TGF-beta receptor 1 (TGF beta R1). However, little was known about connection between inactivation of the TGF beta R1 gene and the presence of CpG methylated promoter in NSCLC. To investigate whether, there is an epigenetic mechanism underlying inactivation of TGF beta R1 in NSCLC, we performed the immunohistochemical and DNA methylation analyzes of TGF beta R1 in tumor and the paired normal tissues from 35 resection specimens. As the first report, the present study demonstrated loss or reduction of TGF beta R1 expression in 11 (31.4%) of 35 NSCLC tissues, suggesting that reduced TGF beta R1 expression could contribute to the development of malignant phenotype of NSCLC, even if no aberrant DNA methylated site was found at sites -362 to -142 of TGF beta R1 promoter region under investigation.