Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas

Kenta Yoshiura, Yae Kanai, Atsushi Ochiai, Yutaka Shimoyama, Takashi Sugimura, Setsuo Hirohashi

Research output: Contribution to journalArticle

563 Citations (Scopus)

Abstract

E-Cadherin, a cell adhesion molecule, which plays a key role in maintaining the epithelial phenotype, is regarded as an invasion-suppressor gene in light of accumulating evidence from in vitro experiments and clinical observations. In an attempt to clarify the mechanism responsible for inactivation of this gene in carcinomas, we investigated the methylation state around the promoter region by digestion of DNA with the methylation- sensitive restriction enzyme Hpa II, as CpG methylation of the promoter has been postulated to be a mechanism of transcriptional inactivation of some genes. We found that E-cadherin expression-negative carcinoma cell lines were accompanied by the hypermethylation state, whereas E-cadherin-positive cell lines were not. Furthermore, treatment of E-cadherin-negative carcinoma cells with the demethylating agent 5-azacytidine resulted in reexpression of the gene and reversion of scattered spindle-shaped cells to cells with epithelial morphology. These results suggest that hypermethylation around the promoter may be a mechanism of E-cadherin inactivation in human carcinomas and that treatment of E-cadherin-inactivated cells with a demethylating agent may cause gene expression reversion leading to epithelial morphogenesis with acquisition of the homophilic cell-cell adhesive property.

Original languageEnglish
Pages (from-to)7416-7419
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number16
DOIs
Publication statusPublished - 1995 Aug 1
Externally publishedYes

Fingerprint

Suppressor Genes
Cadherins
Methylation
Carcinoma
Gene Silencing
Azacitidine
Cell Line
Cell Adhesion Molecules
DNA Methylation
Morphogenesis
Genetic Promoter Regions
Adhesives
Digestion
Epithelial Cells
Phenotype
Gene Expression
Enzymes
Genes

Keywords

  • 5-azacytidine
  • cancer invasion and metastasis
  • cell-cell adhesion

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. / Yoshiura, Kenta; Kanai, Yae; Ochiai, Atsushi; Shimoyama, Yutaka; Sugimura, Takashi; Hirohashi, Setsuo.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 16, 01.08.1995, p. 7416-7419.

Research output: Contribution to journalArticle

Yoshiura, Kenta ; Kanai, Yae ; Ochiai, Atsushi ; Shimoyama, Yutaka ; Sugimura, Takashi ; Hirohashi, Setsuo. / Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. In: Proceedings of the National Academy of Sciences of the United States of America. 1995 ; Vol. 92, No. 16. pp. 7416-7419.
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