Down-regulation of thyroid hormone receptor β1 gene expression in gastric cancer involves promoter methylation

Abstract

Hypermethylation has been shown in the promoter region of the thyroid hormone receptor β1 (TRβ1) gene in several human tumors. However, its role in gastric cancer formation is still unclear. In the study, we analyzed mRNA expression of TRβ1 gene using real-time quantitative PCR (qPCR). A quantitative methylation-specific PCR (Q-MSP) assay was used to determine the methylation status of the TRβ1 gene promoter region in 46 pair-matched gastric neoplastic and adjacent non-neoplastic tissues. The results showed that TRβ1 mRNA expression was significantly reduced in gastric cancer specimens. The methylation of promoter of TRβ1 gene in gastric cancer tissues was significantly higher than in adjacent normal tissues. Promoter hypermethylation of the TRβ1 gene correlated with tumor infiltration, lymph node metastasis, and distant metastasis, but it was not associated with other clinicopathological characteristics. We treated gastric cancer cell lines MKN-45, MKN-28, SGC-7901, NCI-N87, and SNU-1 with 5-Aza-2-deoxycytidine (5-Aza-dC). The results showed the expression of TRβ1 mRNA was increased in MKN-45, MKN-28, SGC-7901, but not increased in NCI-N87 and SNU-1. These results suggest that the TRβ1 gene plays important roles in the development of gastric cancer partially through epigenetic mechanisms.

Keywords: Gastric cancer; Promoter methylation; Quantitative methylation-specific PCR (Q-MSP); Thyroid hormone receptor β1.