title: Estrogens promote cell-cell adhesion of normal and malignant mammary cells through increased desmosome formation.
abstract: The association of estrogen receptor alpha (ERα) expression with differentiated breast tumors presenting a lower metastasis risk could be explained by the estrogen modulation of cell adhesion, motility and invasiveness. Since desmosomes play a crucial role in cell-cell adhesion and may interfere in tumor progression, we studied their regulation by estrogens in human breast cancer and normal mammary cells. Estrogens increased the formation of desmosomes in normal and malignant cells. Furthermore, four desmosomal proteins (desmocollin, γ-catenin, plakophilin and desmoplakin) appeared significantly up-regulated by estrogens in three ERα-expressing cancer cell lines and this effect was reversed by a pure antiestrogen. Finally, silencing of ERα or desmoplakin expression by specific siRNA revealed that estrogen-modulated desmosomal proteins are essential for the estrogenic control of intercellular adhesion. This estrogen modulation of desmosome formation could contribute to the lower invasiveness of ERα-positive tumors and to the integrity of epithelial layers in estrogen target tissues.
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, Université Montpellier 1, Université Montpellier 2, Montpellier, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Maynadier
authors.forename: Monique
authors.initials: M
authors.lastname: Chambon
authors.forename: Ilaria
authors.initials: I
authors.lastname: Basile
authors.forename: Michel
authors.initials: M
authors.lastname: Gleizes
authors.forename: Philippe
authors.initials: P
authors.lastname: Nirde
authors.forename: Magali
authors.initials: M
authors.lastname: Gary-Bobo
authors.forename: Marcel
authors.initials: M
authors.lastname: Garcia
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D051187:Desmocollins / Q000235:genetics / Q000378:metabolism; D051180:Desmoplakins / Q000235:genetics / Q000378:metabolism; D003896:Desmosomes / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D042361:Mammary Glands, Human / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D009361:Neoplasm Invasiveness; D051191:Plakophilins / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation; D051185:gamma Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D051187:Desmocollins; D051180:Desmoplakins; C506487:ESR1 protein, human; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D004967:Estrogens; D051191:Plakophilins; D034741:RNA, Small Interfering; D051185:gamma Catenin