E-Cadherin Expression Is Silenced by DNA Hypermethylation in Human Breast and Prostate Carcinomas

Jeremy R. Graff, James G. Herman, Rena G. Lapidus, Hemi Chopra, Rosa Xu, Paula M. Pitha, Nancy E. Davidson, Stephen B. Baylin, David F. Jarrard, William B. Isaacs

Research output: Contribution to journalArticle

Abstract

Expression of the Ca2+-dependent, homotypic celhcell adhesion molecule, E-cadherin (E-cad), suppresses tumor cell invasion and metastasis in experimental tumor models. Decreased E-cad expression is common in poorly differentiated, advanced-stage carcinomas. These data implicate E-cad as an “invasion suppressor” gene. The mechanism by which E-cad is silenced in advanced stage carcinomas is unclear. In this report, we show that: (a) the 5’ CpG island of E-cad is densely methylated in E-corf-negative breast and prostate carcinoma cell lines and primary breast carcinoma tissue but is unmethylated in normal breast tissue; (b) treatment with the demethylating agent, 5-aza-2’-deoxycytidine, partially restores E-cad RNA and protein levels in E-cad-negative breast and prostate carcinoma cell lines; and (c) an E-cad promoter/CAT construct is expressed in both E-cad-positive and -negative breast and prostate carcinoma cell lines, indicating that these cells have the active transcriptional machinery necessary for E-cad gene expression. Our data demonstrate that frequent loss of E-cad expression in human breast and prostate carcinomas results from hypermethylation of the E-cad promoter region.

Original languageEnglish (US)
Pages (from-to)5195-5199
Number of pages5
JournalCancer Research
Volume55
Issue number22
StatePublished - Nov 15 1995

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Graff, J. R., Herman, J. G., Lapidus, R. G., Chopra, H., Xu, R., Pitha, P. M., Davidson, N. E., Baylin, S. B., Jarrard, D. F., & Isaacs, W. B. (1995). E-Cadherin Expression Is Silenced by DNA Hypermethylation in Human Breast and Prostate Carcinomas. Cancer Research, 55(22), 5195-5199.