title: Secretory Leukocyte Protease Inhibitor (SLPI) expression downregulates E-cadherin, induces β-catenin re-localisation and triggers apoptosis-related events in breast cancer cells.
abstract: BACKGROUND
  Epithelial cadherin (E-cadherin) is involved in cell-cell adhesion through its extracellular domain, whereas the intracellular domain interacts with adaptor proteins, i.e. β-catenin, links E-cadherin to the actin cytoskeleton and participates in signal transduction events. E-cadherin protects mammary epithelial cells from apoptosis and its loss during tumour progression has been documented. Secretory Leukocyte Protease Inhibitor (SLPI) has anti- and pro-tumourigenic activities but its role in breast cancer has not been fully elucidated. Notwithstanding its relevance, how SLPI affects E-cadherin in breast cancer is still unknown. This study evaluated the effect of SLPI upon E-cadherin/β-catenin expression and apoptosis-related markers in murine (F3II) and human (MCF-7) breast tumour cells either treated with exogenous recombinant human SLPI (rhSLPI) or stably transfected with a plasmid encoding its sequence.
  
  
  RESULTS
  Addition of rhSLPI to F3II cells caused a decrease (P < 0.05) in E-cadherin transcript and protein levels. Similar results were observed in SLPI-stable F3II transfectants (2C1), and treatment of 2C1 cells with a siRNA toward SLPI restored E-cadherin to control levels. SLPI-expressing cells showed disruption of E-cadherin/β-catenin complex and increased (P < 0.05) percentage of cells depicting nuclear β-catenin localisation. Associated to these changes, 2C1 cells showed increased Bax/Bcl-2 ratio and p21 protein levels, decreased c-Myc protein levels and decreased Cyclin D1 and Claudin-1 transcript levels. No differences in N- and P-cadherin were observed between SLPI-transfected cells and controls. Addition of rhSLPI to MCF-7 cells or stable transfection with SLPI caused a decrease (P < 0.05) in E-cadherin expression (transcript/protein) and its redistribution to the cytoplasm, as well as β-catenin re-localisation to the cell nucleus.
  
  
  CONCLUSIONS
  Expression of SLPI was associated to a decrease in E-cadherin expression and re-localisation of E-cadherin to the cell cytoplasm and β-catenin to the cell cytoplasm and nucleus, and had pro-apoptotic and cell cycle-arrest effects.
authors.affiliation: Instituto de Biología & Medicina Experimental (IBYME), National Research Council of Argentina (CONICET), Vuelta de Obligado 2490, Buenos Aires, C1428ADN, Argentina.
authors.forename: Marina
authors.initials: M
authors.lastname: Rosso
authors.forename: Lara
authors.initials: L
authors.lastname: Lapyckyj
authors.forename: Nicolás
authors.initials: N
authors.lastname: Amiano
authors.forename: María José
authors.initials: MJ
authors.lastname: Besso
authors.forename: Mercedes
authors.initials: M
authors.lastname: Sánchez
authors.forename: Eduardo
authors.initials: E
authors.lastname: Chuluyan
authors.forename: Mónica Hebe
authors.initials: MH
authors.lastname: Vazquez-Levin
mesh_terms: D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D021381:Protein Transport; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D051176:beta Catenin
keywords: Apoptosis; Cancer; Cell adhesion; Epithelial cadherin; SLPI; β-catenin