Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53

Autores
Andrés, Nancy Carolina; Fermento, María Eugenia; Gandini, Norberto Ariel; Lopez Romero, Alejandro; Ferro, Alejandro; Gonzalez Donna, Lucila; Curino, Alejandro Carlos; Facchinetti, Maria Marta
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The expression of heme oxygenase-1 (HO-1) has been shown to be up-regulated in colorectal cancer (CRC), but the role it plays in this cancer type has not yet been addressed. The aims of this study have been to analyze HO-1 expression in human invasive CRC, evaluate its correlation with clinical and histo-pathological parameters and to investigate the mechanisms through which the enzyme influences tumor progression. We confirmed that HO-1 was over expressed in human invasive CRC and found that the expression of the enzyme was associated with a longer overall survival time. In addition, we observed in a chemically-induced CRC animal model that total and nuclear HO-1 expression increases with tumor progression. Our investigation of the mechanisms involved in HO-1 action in CRC demonstrates that the protein reduces cell viability through induction of cell cycle arrest and apoptosis and, importantly, that a functional p53 tumor suppressor protein is required for these effects. This reduction in cell viability is accompanied by modulation of the levels of p21, p27, and cyclin D1 and by modulation of Akt and PKC pathways. Altogether, our results demonstrate and antitumoral role of HO-1 and points to the importance of p53 status in this antitumor activity.
Fil: Andrés, Nancy Carolina. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); Argentina
Fil: Fermento, María Eugenia. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); Argentina
Fil: Gandini, Norberto Ariel. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); Argentina
Fil: Lopez Romero, Alejandro. IACA Laboratorios; Argentina
Fil: Ferro, Alejandro. Hospital Italiano Regional del Sur. Servicio de Oncología; Argentina
Fil: Gonzalez Donna, Lucila. Hospital Italiano Regional del Sur. Servicio de Oncología; Argentina
Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); Argentina
Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); Argentina
Materia
Heme Oxygenase-1
Colorectal Cancer
P53
Survival
Immunohistochemistry
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:11336/5332
Acceder
id CONICETDig_63d71911564a4b0c48d947b8147017ec
oai_identifier_str oai:ri.conicet.gov.ar:11336/5332
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53Andrés, Nancy CarolinaFermento, María EugeniaGandini, Norberto ArielLopez Romero, AlejandroFerro, AlejandroGonzalez Donna, LucilaCurino, Alejandro CarlosFacchinetti, Maria MartaHeme Oxygenase-1Colorectal CancerP53SurvivalImmunohistochemistryhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The expression of heme oxygenase-1 (HO-1) has been shown to be up-regulated in colorectal cancer (CRC), but the role it plays in this cancer type has not yet been addressed. The aims of this study have been to analyze HO-1 expression in human invasive CRC, evaluate its correlation with clinical and histo-pathological parameters and to investigate the mechanisms through which the enzyme influences tumor progression. We confirmed that HO-1 was over expressed in human invasive CRC and found that the expression of the enzyme was associated with a longer overall survival time. In addition, we observed in a chemically-induced CRC animal model that total and nuclear HO-1 expression increases with tumor progression. Our investigation of the mechanisms involved in HO-1 action in CRC demonstrates that the protein reduces cell viability through induction of cell cycle arrest and apoptosis and, importantly, that a functional p53 tumor suppressor protein is required for these effects. This reduction in cell viability is accompanied by modulation of the levels of p21, p27, and cyclin D1 and by modulation of Akt and PKC pathways. Altogether, our results demonstrate and antitumoral role of HO-1 and points to the importance of p53 status in this antitumor activity.Fil: Andrés, Nancy Carolina. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); ArgentinaFil: Fermento, María Eugenia. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); ArgentinaFil: Gandini, Norberto Ariel. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); ArgentinaFil: Lopez Romero, Alejandro. IACA Laboratorios; ArgentinaFil: Ferro, Alejandro. Hospital Italiano Regional del Sur. Servicio de Oncología; ArgentinaFil: Gonzalez Donna, Lucila. Hospital Italiano Regional del Sur. Servicio de Oncología; ArgentinaFil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); ArgentinaFil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); ArgentinaElsevier2014-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/5332Andrés, Nancy Carolina; Fermento, María Eugenia; Gandini, Norberto Ariel; Lopez Romero, Alejandro; Ferro, Alejandro; et al.; Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53; Elsevier; Experimental and Molecular Pathology; 97; 3; 9-2014; 321-3310014-4800enginfo:eu-repo/semantics/altIdentifier/pmid/25236576info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014480014001531info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yexmp.2014.09.012info:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:03:14Zoai:ri.conicet.gov.ar:11336/5332instacron: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 10:03:14.811CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53
title Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53
spellingShingle Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53
Andrés, Nancy Carolina
Heme Oxygenase-1
Colorectal Cancer
P53
Survival
Immunohistochemistry
title_short Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53
title_full Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53
title_fullStr Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53
title_full_unstemmed Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53
title_sort Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53
dc.creator.none.fl_str_mv Andrés, Nancy Carolina
Fermento, María Eugenia
Gandini, Norberto Ariel
Lopez Romero, Alejandro
Ferro, Alejandro
Gonzalez Donna, Lucila
Curino, Alejandro Carlos
Facchinetti, Maria Marta
author Andrés, Nancy Carolina
author_facet Andrés, Nancy Carolina
Fermento, María Eugenia
Gandini, Norberto Ariel
Lopez Romero, Alejandro
Ferro, Alejandro
Gonzalez Donna, Lucila
Curino, Alejandro Carlos
Facchinetti, Maria Marta
author_role author
author2 Fermento, María Eugenia
Gandini, Norberto Ariel
Lopez Romero, Alejandro
Ferro, Alejandro
Gonzalez Donna, Lucila
Curino, Alejandro Carlos
Facchinetti, Maria Marta
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Heme Oxygenase-1
Colorectal Cancer
P53
Survival
Immunohistochemistry
topic Heme Oxygenase-1
Colorectal Cancer
P53
Survival
Immunohistochemistry
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The expression of heme oxygenase-1 (HO-1) has been shown to be up-regulated in colorectal cancer (CRC), but the role it plays in this cancer type has not yet been addressed. The aims of this study have been to analyze HO-1 expression in human invasive CRC, evaluate its correlation with clinical and histo-pathological parameters and to investigate the mechanisms through which the enzyme influences tumor progression. We confirmed that HO-1 was over expressed in human invasive CRC and found that the expression of the enzyme was associated with a longer overall survival time. In addition, we observed in a chemically-induced CRC animal model that total and nuclear HO-1 expression increases with tumor progression. Our investigation of the mechanisms involved in HO-1 action in CRC demonstrates that the protein reduces cell viability through induction of cell cycle arrest and apoptosis and, importantly, that a functional p53 tumor suppressor protein is required for these effects. This reduction in cell viability is accompanied by modulation of the levels of p21, p27, and cyclin D1 and by modulation of Akt and PKC pathways. Altogether, our results demonstrate and antitumoral role of HO-1 and points to the importance of p53 status in this antitumor activity.
Fil: Andrés, Nancy Carolina. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); Argentina
Fil: Fermento, María Eugenia. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); Argentina
Fil: Gandini, Norberto Ariel. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); Argentina
Fil: Lopez Romero, Alejandro. IACA Laboratorios; Argentina
Fil: Ferro, Alejandro. Hospital Italiano Regional del Sur. Servicio de Oncología; Argentina
Fil: Gonzalez Donna, Lucila. Hospital Italiano Regional del Sur. Servicio de Oncología; Argentina
Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); Argentina
Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Cienti­ficas y Tecnicas. Centro Cientifico Tecnologico Bahi­a Blanca. Instituto de Investigaciones Bioquimicas Bahi­a Blanca (i); Argentina
description The expression of heme oxygenase-1 (HO-1) has been shown to be up-regulated in colorectal cancer (CRC), but the role it plays in this cancer type has not yet been addressed. The aims of this study have been to analyze HO-1 expression in human invasive CRC, evaluate its correlation with clinical and histo-pathological parameters and to investigate the mechanisms through which the enzyme influences tumor progression. We confirmed that HO-1 was over expressed in human invasive CRC and found that the expression of the enzyme was associated with a longer overall survival time. In addition, we observed in a chemically-induced CRC animal model that total and nuclear HO-1 expression increases with tumor progression. Our investigation of the mechanisms involved in HO-1 action in CRC demonstrates that the protein reduces cell viability through induction of cell cycle arrest and apoptosis and, importantly, that a functional p53 tumor suppressor protein is required for these effects. This reduction in cell viability is accompanied by modulation of the levels of p21, p27, and cyclin D1 and by modulation of Akt and PKC pathways. Altogether, our results demonstrate and antitumoral role of HO-1 and points to the importance of p53 status in this antitumor activity.
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/11336/5332
Andrés, Nancy Carolina; Fermento, María Eugenia; Gandini, Norberto Ariel; Lopez Romero, Alejandro; Ferro, Alejandro; et al.; Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53; Elsevier; Experimental and Molecular Pathology; 97; 3; 9-2014; 321-331
0014-4800
url http://hdl.handle.net/11336/5332
identifier_str_mv Andrés, Nancy Carolina; Fermento, María Eugenia; Gandini, Norberto Ariel; Lopez Romero, Alejandro; Ferro, Alejandro; et al.; Heme oxygenase-1 has antitumoral effects in colorectal cancer: Involvement of p53; Elsevier; Experimental and Molecular Pathology; 97; 3; 9-2014; 321-331
0014-4800
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/pmid/25236576
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014480014001531
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yexmp.2014.09.012
info:eu-repo/semantics/altIdentifier/doi/
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
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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