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. 2005 Aug 19;94(5):442–447. doi: 10.1111/j.1349-7006.2003.tb01462.x

MeCP2 and promoter methylation cooperatively regulate E‐cadherin gene expression in colorectal carcinoma

Agus Darwanto 1, Riko Kitazawa 1, Sakan Maeda 1, Sohei Kitazawa 1,✉
PMCID: PMC11160213  PMID: 12824891

Abstract

Reduced expression of E‐cadherin (E‐cad) owing to aberrant 5′CpG island hypermethylation has been regarded as one of the main molecular events involved in the dysfunction of the cell‐cell adhesion system. The molecular mechanisms providing diversity and heterogeneity of E‐cad expression in colorectal carcinoma were explored. In 29 cases of colorectal carcinoma in Indonesia, the expression of E‐cad was analyzed by immunohistochemical staining, the methylation status of the E‐cad promoter was determined by methylation‐specific PCR, and the expression of methyl‐CpG‐binding protein (MeCP) 2 was studied by in situ hybridization. E‐cad expression was strong, and no methylation was observed in normal colon mucosa and most of the well‐differentiated adenocarcinoma. In contrast, both signet‐ring cell carcinoma and mucinous adenocarcinoma showed fully methylated patterns and strong MeCP2 expression. In moderately‐ and poorly‐differentiated adenocarcinomas, however, E‐cad expression was rather heterogeneous, especially at the front of invasion and in the dissociated areas, where loss of MeCP2 expression correlated with E‐cad reexpression even in the presence of E‐cad promoter methylation. We conclude that both CpG methylation of the E‐cad promoter and significant MeCP2 expression cooperatively and epigenetically regulate E‐cad expression in colorectal cancer. (Cancer Sci 2003; 94: 442–447)

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