title: Tumour necrosis factor-alpha-mediated dyscohesion of epithelial cells is associated with disordered expression of cadherin/beta-catenin and disassembly of actin filaments.
abstract: Tumour necrosis factor (TNF)-alpha induced, in a time- and dose-dependent fashion, dyscohesion (cell-cell dissociation) of the endometrial epithelial cells. TNF-alpha impaired the ability of cells to aggregate and to attain compaction. The cell-cell adherent junction is a specialized region of the plasma membrane where cadherin molecules act as adhesion molecules and actin filaments are densely associated with the plasma membrane through a well-developed plasmalemmal undercoat. Dyscohesion induced by TNF-alpha was associated with the disordered expression of cadherin/beta-catenin at the sites of cell-cell contact. In addition, within the time-frame that dyscohesion was induced, TNF-alpha down-regulated the expression of actin mRNA only at 100 ng/ml without modulating the overall amount of actin protein, its beta-isoform or the amount of ribosylated actin. However, TNF-alpha-mediated dyscohesion of epithelial cells was associated with loss of plasmalemmal undercoat as well as intracytoplasmic aggregates of F-actin and a simultaneous increase in G-actin. The effect of cytochalasin-B, which disrupts actin filaments on cell-cell binding, was less pronounced than the effect of TNF-alpha, suggesting that the effect of this cytokine on dyscohesion is not solely dependent on the disassembly of actin filaments. These findings show that the induction of disordered expression of adhesion molecules, as well as disassembly of actin filaments, are implicated in the dyscohesion induced by TNF-alpha.
authors.affiliation: Department of Pathology, University of South Florida Health Sciences Center, Tampa 33612, USA.
authors.forename: S
authors.initials: S
authors.lastname: Tabibzadeh
authors.forename: Q F
authors.initials: QF
authors.lastname: Kong
authors.forename: S
authors.initials: S
authors.lastname: Kapur
authors.forename: P G
authors.initials: PG
authors.lastname: Satyaswaroop
authors.forename: K
authors.initials: K
authors.lastname: Aktories
mesh_terms: D000199:Actins / Q000502:physiology*; D015820:Cadherins / Q000096:biosynthesis*; D002450:Cell Communication / Q000187:drug effects*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D003599:Cytoskeleton / Q000187:drug effects; D004717:Endometrium / Q000502:physiology*; D004848:Epithelium / Q000502:physiology; D005260:Female; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D051176:beta Catenin
chemical_list: D000199:Actins; C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin