title: E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas.
abstract: 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) and 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 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.
authors.affiliation: Johns Hopkins Oncology Center, Johns Hopkins University Medical Center, Baltimore, Maryland 21231, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Graff
authors.forename: J G
authors.initials: JG
authors.lastname: Herman
authors.forename: R G
authors.initials: RG
authors.lastname: Lapidus
authors.forename: H
authors.initials: H
authors.lastname: Chopra
authors.forename: R
authors.initials: R
authors.lastname: Xu
authors.forename: D F
authors.initials: DF
authors.lastname: Jarrard
authors.forename: W B
authors.initials: WB
authors.lastname: Isaacs
authors.forename: P M
authors.initials: PM
authors.lastname: Pitha
authors.forename: N E
authors.initials: NE
authors.lastname: Davidson
authors.forename: S B
authors.initials: SB
authors.lastname: Baylin
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D004247:DNA / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008745:Methylation; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; D004247:DNA