title: Kepone (chlordecone) disrupts adherens junctions in human breast epithelial cells cultured on matrigel.
abstract: Perturbations in cell-extracellular matrix (ECM) interactions are a consistent feature of mammary tumors and cells in culture. We have utilized MCF-10ATG3B human breast epithelial cells to examine whether the organochlorine Kepone induces alterations in cell adhesion molecules important to cell-cell and cell-ECM interactions. Kepone effects on the levels and association of proteins involved in adherens junctions or desmosomes were examined using immunoblot analysis and immunoprecipitation. MCF-10ATG3B cells cultured on an ECM of Matrigel form lattice-like structures that are disrupted with 0.1 and 1 microM Kepone. E-cadherin protein levels decreased significantly by approximately 23% and approximately 69% following treatment with 0.1 and 1.0 microM Kepone, respectively, relative to solvent-treated cells. Desmoglein and alpha- and gamma-catenin levels did not vary significantly with Kepone. Beta-catenin protein levels decreased significantly by approximately 37%, 36% and 53% at 0.01, 0.1 and 1.0 microM Kepone, respectively. E-cadherin-gamma-catenin association was disrupted with 0.1 and 1.0 microM Kepone. Thus, Kepone disrupts cellular architecture, specifically E-cadherin-gamma-catenin containing adherens junctions, which may ultimately affect cellular phenotype.
authors.affiliation: Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48201, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Starcevic
authors.forename: S
authors.initials: S
authors.lastname: Bortolin
authors.forename: K J
authors.initials: KJ
authors.lastname: Woodcroft
authors.forename: R F
authors.initials: RF
authors.lastname: Novak
mesh_terms: D022005:Adherens Junctions / Q000187:drug effects* / Q000648:ultrastructure; D001940:Breast / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001943:Breast Neoplasms / Q000139:chemically induced; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007631:Chlordecone / Q000009:adverse effects / Q000494:pharmacology*; D003094:Collagen; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes / Q000187:drug effects / Q000648:ultrastructure; D004338:Drug Combinations; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000502:physiology; D005260:Female; D006801:Humans; D007797:Laminin; D010573:Pesticide Residues / Q000009:adverse effects / Q000494:pharmacology*; D011509:Proteoglycans; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin
chemical_list: C495273:CTNNA1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051182:Desmogleins; D051180:Desmoplakins; D004338:Drug Combinations; C495292:JUP protein, human; D007797:Laminin; D010573:Pesticide Residues; D011509:Proteoglycans; D015534:Trans-Activators; D051178:alpha Catenin; D051176:beta Catenin; D051185:gamma Catenin; C059485:matrigel; D003094:Collagen; D007631:Chlordecone