Secretory leukocyte protease inhibitor (slpi) expression downregulates E-cadherin, induces β-catenin re-localization and triggers apoptosis-related events in breast cancer cells

Autores
Rosso, Marina; Lapyckyj, Lara; Amiano, Nicolás Oscar; Besso, María José; Sanchez, Mercedes Leonor; Chuluyan, Hector Eduardo; Vazquez, Monica Hebe
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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. 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.
Fil: Rosso, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Lapyckyj, Lara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Amiano, Nicolás Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina
Fil: Besso, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Sanchez, Mercedes Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina
Fil: Chuluyan, Hector Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina
Fil: Vazquez, Monica Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Materia
Apoptosis
Beta-Catenina
Cancer
Cell Adhesion
Ephitelial Cadherin
Slpi
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/14168
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/14168
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Secretory leukocyte protease inhibitor (slpi) expression downregulates E-cadherin, induces β-catenin re-localization and triggers apoptosis-related events in breast cancer cellsRosso, MarinaLapyckyj, LaraAmiano, Nicolás OscarBesso, María JoséSanchez, Mercedes LeonorChuluyan, Hector EduardoVazquez, Monica HebeApoptosisBeta-CateninaCancerCell AdhesionEphitelial CadherinSlpihttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1BACKGROUND 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. 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.Fil: Rosso, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Lapyckyj, Lara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Amiano, Nicolás Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; ArgentinaFil: Besso, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Sanchez, Mercedes Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; ArgentinaFil: Chuluyan, Hector Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; ArgentinaFil: Vazquez, Monica Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaWiley2014-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/14168Rosso, Marina; Lapyckyj, Lara; Amiano, Nicolás Oscar; Besso, María José; Sanchez, Mercedes Leonor; et al.; Secretory leukocyte protease inhibitor (slpi) expression downregulates E-cadherin, induces β-catenin re-localization and triggers apoptosis-related events in breast cancer cells; Wiley; Biology Of The Cell; 106; 9; 9-2014; 308-3220248-4900enginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/boc.201300075/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1111/boc.201300075info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:28:46Zoai:ri.conicet.gov.ar:11336/14168instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:28:47.048CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Secretory leukocyte protease inhibitor (slpi) expression downregulates E-cadherin, induces β-catenin re-localization and triggers apoptosis-related events in breast cancer cells
title Secretory leukocyte protease inhibitor (slpi) expression downregulates E-cadherin, induces β-catenin re-localization and triggers apoptosis-related events in breast cancer cells
spellingShingle Secretory leukocyte protease inhibitor (slpi) expression downregulates E-cadherin, induces β-catenin re-localization and triggers apoptosis-related events in breast cancer cells
Rosso, Marina
Apoptosis
Beta-Catenina
Cancer
Cell Adhesion
Ephitelial Cadherin
Slpi
title_short Secretory leukocyte protease inhibitor (slpi) expression downregulates E-cadherin, induces β-catenin re-localization and triggers apoptosis-related events in breast cancer cells
title_full Secretory leukocyte protease inhibitor (slpi) expression downregulates E-cadherin, induces β-catenin re-localization and triggers apoptosis-related events in breast cancer cells
title_fullStr Secretory leukocyte protease inhibitor (slpi) expression downregulates E-cadherin, induces β-catenin re-localization and triggers apoptosis-related events in breast cancer cells
title_full_unstemmed Secretory leukocyte protease inhibitor (slpi) expression downregulates E-cadherin, induces β-catenin re-localization and triggers apoptosis-related events in breast cancer cells
title_sort Secretory leukocyte protease inhibitor (slpi) expression downregulates E-cadherin, induces β-catenin re-localization and triggers apoptosis-related events in breast cancer cells
dc.creator.none.fl_str_mv Rosso, Marina
Lapyckyj, Lara
Amiano, Nicolás Oscar
Besso, María José
Sanchez, Mercedes Leonor
Chuluyan, Hector Eduardo
Vazquez, Monica Hebe
author Rosso, Marina
author_facet Rosso, Marina
Lapyckyj, Lara
Amiano, Nicolás Oscar
Besso, María José
Sanchez, Mercedes Leonor
Chuluyan, Hector Eduardo
Vazquez, Monica Hebe
author_role author
author2 Lapyckyj, Lara
Amiano, Nicolás Oscar
Besso, María José
Sanchez, Mercedes Leonor
Chuluyan, Hector Eduardo
Vazquez, Monica Hebe
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Apoptosis
Beta-Catenina
Cancer
Cell Adhesion
Ephitelial Cadherin
Slpi
topic Apoptosis
Beta-Catenina
Cancer
Cell Adhesion
Ephitelial Cadherin
Slpi
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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. 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.
Fil: Rosso, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Lapyckyj, Lara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Amiano, Nicolás Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina
Fil: Besso, María José. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Sanchez, Mercedes Leonor. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina
Fil: Chuluyan, Hector Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Medicina. Cátedra de Farmacología; Argentina
Fil: Vazquez, Monica Hebe. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
description 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. 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.
publishDate 2014
dc.date.none.fl_str_mv 2014-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/14168
Rosso, Marina; Lapyckyj, Lara; Amiano, Nicolás Oscar; Besso, María José; Sanchez, Mercedes Leonor; et al.; Secretory leukocyte protease inhibitor (slpi) expression downregulates E-cadherin, induces β-catenin re-localization and triggers apoptosis-related events in breast cancer cells; Wiley; Biology Of The Cell; 106; 9; 9-2014; 308-322
0248-4900
url http://hdl.handle.net/11336/14168
identifier_str_mv Rosso, Marina; Lapyckyj, Lara; Amiano, Nicolás Oscar; Besso, María José; Sanchez, Mercedes Leonor; et al.; Secretory leukocyte protease inhibitor (slpi) expression downregulates E-cadherin, induces β-catenin re-localization and triggers apoptosis-related events in breast cancer cells; Wiley; Biology Of The Cell; 106; 9; 9-2014; 308-322
0248-4900
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1111/boc.201300075/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1111/boc.201300075
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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