Increased methylation of promotor region suppresses expression of MUC2 gene in colon carcinoma cells]

MUC2 is known to be the main intestinal mucin carrying the carbohydrate moiety sialyl-Le(x), which interacts with the endothelial molecule E-selectin. This interaction may contribute to the extravasation of tumor cells and thus to the metastatic process. We analysed MUC2 expression in normal colonic, carcinomatous and metastatic tissue and the regulation of MUC2 gene expression. In metastases MUC2 expression was significantly lower than in normal tissue and primary tumors and seems not to be related to the metastatic process. In several colorectal carcinoma cell lines the methylation of the 5'-flanking region of MUC2 correlated with the suppression of the MUC2 gene. The increase of the MUC2 expression after the inhibition of the methylation with 5-aza-2' deoxycytidine strongly support the notion that the suppression of MUC2 gene is causally related to the methylation of the promoter.