Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-77 cells

Autores
Boland, Ricardo Leopoldo; Scodelaro Bilbao, Paola Gabriela
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Forkhead Box-O (FoxO) transcription factors regulate the expression of many genes involved in suppression. Released nucleotides can regulate intracellular signaling pathways through membrane-bound purinergic receptors, to promote or prevent malignant cell transformation We studied the role of extracellular ATP in the modulation of Forkhead Box O (FoxO) transcription factors and of cell cycle progression in MCF-7 breast cancer cells. Methods: Western blot analysis, cell transfections with siRNA against Akt, immunocytochemistry, subcellular fractionation studies and flow cytometry analysis were performed. Results: ATP induced the phosphorylation of FoxO1/3a at threonine 24/32, whereas reduced the expression of FoxO1. In addition, ATP increased the expression of the cyclins D1 and D3 and down-regulated the cell cycle inhibitory proteins p21Cip1 and p27Kip1. The use of the phosphatidylinositol 3 kinase (PI3K) inhibitor, Ly294002, and/or of siRNA to reduce the expression of the serine/threonine kinase Akt showed that these effects are mediated by the PI3K/Akt signaling pathway. ATP induced the translocation of FoxO3a from the nucleus to the cytoplasm. Also, ATP increased the number of cells in the S phase of cell cycle; this effect was reverted by the use of Ly294002 and the proteasome inhibitor bortezomib. Conclusion: Extracellular ATP induces the inactivation of FoxO transcription factors and cell cycle progression through the PI3K/Akt pathway in MCF-7 cells. General significance: These findings provide new molecular basis for further understanding the mechanisms involved in ATP signal transduction in breast cancer cells, and should be considered for the development of effective breast cancer therapeutic strategies.
Fil: Boland, Ricardo Leopoldo. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida(i); Argentina
Fil: Scodelaro Bilbao, Paola Gabriela. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida(i); Argentina
Materia
Extracellular Atp
Foxo
Cell Cycle
Pi3k/Akt
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/7581
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/7581
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-77 cellsBoland, Ricardo LeopoldoScodelaro Bilbao, Paola GabrielaExtracellular AtpFoxoCell CyclePi3k/Akthttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: Forkhead Box-O (FoxO) transcription factors regulate the expression of many genes involved in suppression. Released nucleotides can regulate intracellular signaling pathways through membrane-bound purinergic receptors, to promote or prevent malignant cell transformation We studied the role of extracellular ATP in the modulation of Forkhead Box O (FoxO) transcription factors and of cell cycle progression in MCF-7 breast cancer cells. Methods: Western blot analysis, cell transfections with siRNA against Akt, immunocytochemistry, subcellular fractionation studies and flow cytometry analysis were performed. Results: ATP induced the phosphorylation of FoxO1/3a at threonine 24/32, whereas reduced the expression of FoxO1. In addition, ATP increased the expression of the cyclins D1 and D3 and down-regulated the cell cycle inhibitory proteins p21Cip1 and p27Kip1. The use of the phosphatidylinositol 3 kinase (PI3K) inhibitor, Ly294002, and/or of siRNA to reduce the expression of the serine/threonine kinase Akt showed that these effects are mediated by the PI3K/Akt signaling pathway. ATP induced the translocation of FoxO3a from the nucleus to the cytoplasm. Also, ATP increased the number of cells in the S phase of cell cycle; this effect was reverted by the use of Ly294002 and the proteasome inhibitor bortezomib. Conclusion: Extracellular ATP induces the inactivation of FoxO transcription factors and cell cycle progression through the PI3K/Akt pathway in MCF-7 cells. General significance: These findings provide new molecular basis for further understanding the mechanisms involved in ATP signal transduction in breast cancer cells, and should be considered for the development of effective breast cancer therapeutic strategies.Fil: Boland, Ricardo Leopoldo. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida(i); ArgentinaFil: Scodelaro Bilbao, Paola Gabriela. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida(i); ArgentinaElsevier2013-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/7581Boland, Ricardo Leopoldo; Scodelaro Bilbao, Paola Gabriela; Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-77 cells; Elsevier; Biochimica Et Biophysica Acta- General Subjects; 1830; 10; 9-2013; 4456-44690304-4165enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0304416513002304info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbagen.2013.05.034info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:48:05Zoai:ri.conicet.gov.ar:11336/7581instacron: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:34982025-09-03 09:48:05.369CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-77 cells
title Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-77 cells
spellingShingle Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-77 cells
Boland, Ricardo Leopoldo
Extracellular Atp
Foxo
Cell Cycle
Pi3k/Akt
title_short Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-77 cells
title_full Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-77 cells
title_fullStr Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-77 cells
title_full_unstemmed Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-77 cells
title_sort Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-77 cells
dc.creator.none.fl_str_mv Boland, Ricardo Leopoldo
Scodelaro Bilbao, Paola Gabriela
author Boland, Ricardo Leopoldo
author_facet Boland, Ricardo Leopoldo
Scodelaro Bilbao, Paola Gabriela
author_role author
author2 Scodelaro Bilbao, Paola Gabriela
author2_role author
dc.subject.none.fl_str_mv Extracellular Atp
Foxo
Cell Cycle
Pi3k/Akt
topic Extracellular Atp
Foxo
Cell Cycle
Pi3k/Akt
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: Forkhead Box-O (FoxO) transcription factors regulate the expression of many genes involved in suppression. Released nucleotides can regulate intracellular signaling pathways through membrane-bound purinergic receptors, to promote or prevent malignant cell transformation We studied the role of extracellular ATP in the modulation of Forkhead Box O (FoxO) transcription factors and of cell cycle progression in MCF-7 breast cancer cells. Methods: Western blot analysis, cell transfections with siRNA against Akt, immunocytochemistry, subcellular fractionation studies and flow cytometry analysis were performed. Results: ATP induced the phosphorylation of FoxO1/3a at threonine 24/32, whereas reduced the expression of FoxO1. In addition, ATP increased the expression of the cyclins D1 and D3 and down-regulated the cell cycle inhibitory proteins p21Cip1 and p27Kip1. The use of the phosphatidylinositol 3 kinase (PI3K) inhibitor, Ly294002, and/or of siRNA to reduce the expression of the serine/threonine kinase Akt showed that these effects are mediated by the PI3K/Akt signaling pathway. ATP induced the translocation of FoxO3a from the nucleus to the cytoplasm. Also, ATP increased the number of cells in the S phase of cell cycle; this effect was reverted by the use of Ly294002 and the proteasome inhibitor bortezomib. Conclusion: Extracellular ATP induces the inactivation of FoxO transcription factors and cell cycle progression through the PI3K/Akt pathway in MCF-7 cells. General significance: These findings provide new molecular basis for further understanding the mechanisms involved in ATP signal transduction in breast cancer cells, and should be considered for the development of effective breast cancer therapeutic strategies.
Fil: Boland, Ricardo Leopoldo. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida(i); Argentina
Fil: Scodelaro Bilbao, Paola Gabriela. Universidad Nacional del Sur; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Bahía Blanca. Centro de Recursos Naturales Renovables de la Zona Semiárida(i); Argentina
description Background: Forkhead Box-O (FoxO) transcription factors regulate the expression of many genes involved in suppression. Released nucleotides can regulate intracellular signaling pathways through membrane-bound purinergic receptors, to promote or prevent malignant cell transformation We studied the role of extracellular ATP in the modulation of Forkhead Box O (FoxO) transcription factors and of cell cycle progression in MCF-7 breast cancer cells. Methods: Western blot analysis, cell transfections with siRNA against Akt, immunocytochemistry, subcellular fractionation studies and flow cytometry analysis were performed. Results: ATP induced the phosphorylation of FoxO1/3a at threonine 24/32, whereas reduced the expression of FoxO1. In addition, ATP increased the expression of the cyclins D1 and D3 and down-regulated the cell cycle inhibitory proteins p21Cip1 and p27Kip1. The use of the phosphatidylinositol 3 kinase (PI3K) inhibitor, Ly294002, and/or of siRNA to reduce the expression of the serine/threonine kinase Akt showed that these effects are mediated by the PI3K/Akt signaling pathway. ATP induced the translocation of FoxO3a from the nucleus to the cytoplasm. Also, ATP increased the number of cells in the S phase of cell cycle; this effect was reverted by the use of Ly294002 and the proteasome inhibitor bortezomib. Conclusion: Extracellular ATP induces the inactivation of FoxO transcription factors and cell cycle progression through the PI3K/Akt pathway in MCF-7 cells. General significance: These findings provide new molecular basis for further understanding the mechanisms involved in ATP signal transduction in breast cancer cells, and should be considered for the development of effective breast cancer therapeutic strategies.
publishDate 2013
dc.date.none.fl_str_mv 2013-09
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/11336/7581
Boland, Ricardo Leopoldo; Scodelaro Bilbao, Paola Gabriela; Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-77 cells; Elsevier; Biochimica Et Biophysica Acta- General Subjects; 1830; 10; 9-2013; 4456-4469
0304-4165
url http://hdl.handle.net/11336/7581
identifier_str_mv Boland, Ricardo Leopoldo; Scodelaro Bilbao, Paola Gabriela; Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-77 cells; Elsevier; Biochimica Et Biophysica Acta- General Subjects; 1830; 10; 9-2013; 4456-4469
0304-4165
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0304416513002304
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbagen.2013.05.034
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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 13.13397

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