title: Mechanisms of inactivation of E-cadherin in breast cancer cell lines.
abstract: Loss of E-cadherin (CDH1) function is thought to contribute to progression in breast cancer and other solid tumors by increasing proliferation, invasion, and/or metastasis. In some cases, the restoration of CDH1 function may be an important therapeutic option. This possibility will depend on the mechanism by which CDH1 is inactivated. Here we present analyses of CDH1 expression, genetic mutation, and promoter methylation in CDH1 in 10 commonly used breast cancer cell lines. Five cell lines (BT-474, MCF-7, MDA-MB-361, MDA-MB-468, and T-47D) expressed CDH1 and were genetically normal. Five others (SK-BR-3, 600 MPE, MDA-MB-134 IV, CAMA1, and MDA-MB-435) did not express CDH1. Fluorescence in situ hybridization analyses of each of these cell lines showed evidence for the physical deletion of one allele of CDH1, and three cell lines were found to carry homozygous deletions. SK-BR-3 was deleted from exon 12 through the promoter; exon 6 was deleted in MDA-MB-134 IV cells, and 600 MPE cells carried a 21-bp deletion in the splicing acceptor site for exon 9. CAMA1 seemed to have been inactivated through promoter methylation. No explanation was found for the inactivation of CDH1 in MDA-MB-435.
authors.affiliation: University of California San Francisco Cancer Center, 94143-0808, USA.
authors.forename: S
authors.initials: S
authors.lastname: Hiraguri
authors.forename: T
authors.initials: T
authors.lastname: Godfrey
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
authors.forename: J
authors.initials: J
authors.lastname: Graff
authors.forename: C
authors.initials: C
authors.lastname: Collins
authors.forename: L
authors.initials: L
authors.lastname: Shayesteh
authors.forename: N
authors.initials: N
authors.lastname: Doggett
authors.forename: K
authors.initials: K
authors.lastname: Johnson
authors.forename: M
authors.initials: M
authors.lastname: Wheelock
authors.forename: J
authors.initials: J
authors.lastname: Herman
authors.forename: S
authors.initials: S
authors.lastname: Baylin
authors.forename: D
authors.initials: D
authors.lastname: Pinkel
authors.forename: J
authors.initials: J
authors.lastname: Gray
mesh_terms: D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D015820:Cadherins; D017931:DNA Primers