E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas
Graff, J.R.; Herman, J.G.; Lapidus, R.G.; Chopra, H.; Xu, R.; Jarrard, D.F.; Isaacs, W.B.; Pitha, P.M.; Davidson, N.E.; Baylin, S.B.
Cancer Research 55(22): 5195-5199
1995
ISSN/ISBN: 0008-5472 PMID: 7585573 Document Number: 451304
Expression of the Ca-2+-dependent, homotypic cell:cell 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-cad-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.