Down-regulation of B-Cell Translocation Gene 1 by Promoter Methylation in Colorectal Carcinoma

Abstract

Background: B-cell translocation gene 1 (BTG1) acts as a tumour suppressor in human malignancies. However, the precise mechanism of BTG1 down-regulation in colorectal carcinoma (CRC) remains unclear. We analyzed BTG1 expression in CRC cell lines and tissues and investigated the mechanism underlying the observed alterations.

Materials and methods: Real-time polymerase chain reaction (PCR) and western blot analyses were performed to analyze BTG1 expression in CRC cell lines. The methylation status of the BTG1 promoter region in cell lines was determined by methylation-specific PCR, and the effect of demethylation on BTG1 expression was explored with 5-aza-deoxycytidine treatment. BTG1 protein expression in CRC tissue samples was evaluated using immunostaining.

Results: CRC cell lines and tissue samples expressed lower levels of BTG1 compared to controls, and BTG1 levels were significantly lower in metastatic than primary CRC. In BTG1-down-regulated CRC cell lines, the BTG1 promoter was highly methylated, and 5-aza-deoxycytidine significantly restored BTG1 expression.

Conclusion: BTG1 down-regulation in CRC occurs through epigenetic repression, which is involved in the development and progression of CRC.

Keywords: B-cell translocation gene 1; Colon; colorectal carcinoma; down-regulation; promoter methylation.