Regulation of the intestinal mucin MUC2 gene expression in vivo: evidence for the role of promoter methylation

In the present work we investigated the in vivo regulation of the mucin gen e MUC2, which is overexpressed in all mucinous colorectal carcinomas. The i nhibition of methylation by 5-azadeoxycytidine induces de novo expression o f MUC2 in the colon carcinoma cell line COLO 205. The expression is retaine d in xenograft tissue and the cells give rise to MUC2-expressing tumours in nude mice. The strong expression of MUC2 in the normal human goblet cells and in the tissue of human mucinous colorectal carcinomas is associated wit h the average methylation of about 50% at every investigated CpG site of th e MUC2 promoter. In contrast, MUC2 promoter in the non-expressing normal co lumnar cells and in the non-mucinous carcinoma tissue is methylated to near ly 100%. These data show that (i) low methylation of MUC2 promoter is assoc iated with MUC2 expression in vivo and (ii) the pattern of MUC2 promoter me thylation in the normal goblet or columnar cells most closely resembles tha t in mucinous or non-mucinous colorectal carcinomas, respectively. They ind icate that MUC2 expression in vivo is regulated by promoter methylation and support the hypothesis that cells with goblet-like differentiation give ri se to mucinous colonic carcinomas. (C) 2001 Elsevier Science Ireland Ltd. A ll rights reserved.