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

Cancer Sci. 2003 May;94(5):442-7. doi: 10.1111/j.1349-7006.2003.tb01462.x.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma, Mucinous / genetics
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / pathology
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Carcinoma, Signet Ring Cell / genetics
  • Carcinoma, Signet Ring Cell / metabolism
  • Carcinoma, Signet Ring Cell / pathology
  • Chromosomal Proteins, Non-Histone*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • CpG Islands
  • DNA Methylation*
  • DNA Probes
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • In Situ Hybridization
  • Methyl-CpG-Binding Protein 2
  • Promoter Regions, Genetic*
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / metabolism
  • Repressor Proteins*
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Tumor Cells, Cultured


  • Cadherins
  • Chromosomal Proteins, Non-Histone
  • DNA Probes
  • DNA-Binding Proteins
  • MECP2 protein, human
  • Methyl-CpG-Binding Protein 2
  • RNA, Messenger
  • RNA, Neoplasm
  • Repressor Proteins