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Secretory Leukocyte Protease Inhibitor (SLPI) expression downregulates E‐cadherin, induces β‐catenin re‐localisation and triggers apoptosis‐related events in breast cancer cells
Author(s) -
Rosso Marina,
Lapyckyj Lara,
Amiano Nicolás,
Besso María José,
Sánchez Mercedes,
Chuluyan Eduardo,
VazquezLevin Mónica Hebe
Publication year - 2014
Publication title -
biology of the cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 85
eISSN - 1768-322X
pISSN - 0248-4900
DOI - 10.1111/boc.201300075
Subject(s) - biology , slpi , apoptosis , cadherin , microbiology and biotechnology , cancer research , cancer cell , catenin , protease , protease inhibitor (pharmacology) , cancer , immunology , cell , signal transduction , enzyme , genetics , biochemistry , inflammation , wnt signaling pathway , human immunodeficiency virus (hiv) , antiretroviral therapy , viral load
Background Information 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. S ecretory L eukocyte P rotease I nhibitor (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.