IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Secretory Leukocyte Protease Inhibitor (SLPI) Expression Downregulates E-Cadherin, Induces β-catenin Re-Localization and Triggers Apoptosis-Related Events in Breast Cancer Cells
Autor/es:
ROSSO, M.; LAPYCKYL, L.; AMIANO, N.; BESSO, M. J.; SANCHEZ, M. L.; CHULUYAN, E.; VAZQUEZ-LEVIN, M.
Revista:
BIOLOGY OF THE CELL
Editorial:
PORTLAND PRESS LTD
Referencias:
Lugar: Londres; Año: 2014 vol. 106 p. 1 - 15
ISSN:
0248-4900
Resumen:
Background Information. Epithelial cadherin (E-cadherin) is involved in cell?cell adhesion through its extracellulardomain, whereas the intracellular domain interacts with adaptor proteins, i.e. β-catenin, links E-cadherin to theactin cytoskeleton and participates in signal transduction events. E-cadherin protects mammary epithelial cellsfrom apoptosis and its loss during tumour progression has been documented. Secretory Leukocyte ProteaseInhibitor (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 evaluatedthe 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 transfectedwith 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 siRNAtoward 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. Associatedto these changes, 2C1 cells showed increased Bax/Bcl-2 ratio and p21 protein levels, decreased c-Myc proteinlevels and decreased Cyclin D1 and Claudin-1 transcript levels. No differences in N- and P-cadherin were observedbetween SLPI-transfected cells and controls. Addition of rhSLPI to MCF-7 cells or stable transfection with SLPIcaused 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 ofE-cadherin to the cell cytoplasm and β-catenin to the cell cytoplasm and nucleus, and had pro-apoptotic and cellcycle-arrest effects.