Hemeoxigenase-1 Genetic Variants Effects On Breast Cancer Progression

Autores
Schweitzer, Karen; Alonso, Exequiel Gonzalo; Fernández Chávez, Lucía; Colo, Georgina Pamela; Alonso, Eliana Noelia; Ferronato, María Julia; Fermento, María Eugenia; Curino, Alejandro Carlos; Facchinetti, Maria Marta
Año de publicación
2024
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Hemoxygenase-1 (HO-1) is a microsomal enzyme that catalyzes the degradation of the heme group (canonical role) and can be cleaved at its C-terminal end, followed by translocation to the nucleus, to perform functions at the transcriptional level (non-canonical role). Our laboratory has already demonstrated that HO-1 has antitumoral activity in breast cancer (BC) and that nuclear HO-1 is not enzymatically active. The aim of this work was to study the effect of genetic overexpression of HO-1 variants on cellular processes related to cancer progression, and the molecular mechanisms through which HO-1 modulates the cellular processes investigated. To accomplish this goal, we used the hormone- dependent BC cell line T47D and the triple-negative BC cell lines 4T1 and MDA-MB-231. These cell lines were stably transfected with plasmids overexpressing the HO-1 variants (full-length (FL-HO1), full-length without enzymatic activity (H25A-HO1) and truncated (T-HO1)). We observed significant differences in cell viability between wild-type (WT) cells and cells overexpressing HO-1 variants in the three cell lines evaluated (p<0.05, two-way ANOVA). We found that the WT cell line displays a higher rate of proliferation than those that overexpress FL in the three cell lines analyzed. However, the T-HO1 form behaves differently among cell lines, displaying more proliferative activity in 4T1 and MDA- MB-231 than in T47D cells. The H25A form appear to behave in the same way among cell lines, showing a similar phenotype to WT cells. These results indicate that the overexpression of HO-1 FL seems to display an anti-tumor role. The behavior of the H25A and the T-HO1 variants would indicate that the anti-tumor behavior is the result of both HO-1 enzymatic activity and its nuclear localization. In addition, cell line hormone-dependency would also contribute to the differential effects. Altogether, these results provide evidence of the canonical and non-canonical roles of HO-1 in BC.
Fil: Schweitzer, Karen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Alonso, Exequiel Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Fernández Chávez, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Colo, Georgina Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Alonso, Eliana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Ferronato, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Fermento, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Buenos Aires Breast Cancer Symposium
Buenos Aires
Argentina
Universidad de Buenos Aires
Materia
HO-1
BREAST CANCER
GENETIC VARIANTS
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:11336/277785
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Hemeoxigenase-1 Genetic Variants Effects On Breast Cancer ProgressionSchweitzer, KarenAlonso, Exequiel GonzaloFernández Chávez, LucíaColo, Georgina PamelaAlonso, Eliana NoeliaFerronato, María JuliaFermento, María EugeniaCurino, Alejandro CarlosFacchinetti, Maria MartaHO-1BREAST CANCERGENETIC VARIANTShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Hemoxygenase-1 (HO-1) is a microsomal enzyme that catalyzes the degradation of the heme group (canonical role) and can be cleaved at its C-terminal end, followed by translocation to the nucleus, to perform functions at the transcriptional level (non-canonical role). Our laboratory has already demonstrated that HO-1 has antitumoral activity in breast cancer (BC) and that nuclear HO-1 is not enzymatically active. The aim of this work was to study the effect of genetic overexpression of HO-1 variants on cellular processes related to cancer progression, and the molecular mechanisms through which HO-1 modulates the cellular processes investigated. To accomplish this goal, we used the hormone- dependent BC cell line T47D and the triple-negative BC cell lines 4T1 and MDA-MB-231. These cell lines were stably transfected with plasmids overexpressing the HO-1 variants (full-length (FL-HO1), full-length without enzymatic activity (H25A-HO1) and truncated (T-HO1)). We observed significant differences in cell viability between wild-type (WT) cells and cells overexpressing HO-1 variants in the three cell lines evaluated (p<0.05, two-way ANOVA). We found that the WT cell line displays a higher rate of proliferation than those that overexpress FL in the three cell lines analyzed. However, the T-HO1 form behaves differently among cell lines, displaying more proliferative activity in 4T1 and MDA- MB-231 than in T47D cells. The H25A form appear to behave in the same way among cell lines, showing a similar phenotype to WT cells. These results indicate that the overexpression of HO-1 FL seems to display an anti-tumor role. The behavior of the H25A and the T-HO1 variants would indicate that the anti-tumor behavior is the result of both HO-1 enzymatic activity and its nuclear localization. In addition, cell line hormone-dependency would also contribute to the differential effects. Altogether, these results provide evidence of the canonical and non-canonical roles of HO-1 in BC.Fil: Schweitzer, Karen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Alonso, Exequiel Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Fernández Chávez, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Colo, Georgina Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Alonso, Eliana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Ferronato, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Fermento, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaBuenos Aires Breast Cancer SymposiumBuenos AiresArgentinaUniversidad de Buenos AiresUniversidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales2024info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectSimposioBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/277785Hemeoxigenase-1 Genetic Variants Effects On Breast Cancer Progression; Buenos Aires Breast Cancer Symposium; Buenos Aires; Argentina; 2024; 98-98CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://ba-bcsymposium.com/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-23T13:55:10Zoai:ri.conicet.gov.ar:11336/277785instacron: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:34982025-12-23 13:55:11.253CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hemeoxigenase-1 Genetic Variants Effects On Breast Cancer Progression
title Hemeoxigenase-1 Genetic Variants Effects On Breast Cancer Progression
spellingShingle Hemeoxigenase-1 Genetic Variants Effects On Breast Cancer Progression
Schweitzer, Karen
HO-1
BREAST CANCER
GENETIC VARIANTS
title_short Hemeoxigenase-1 Genetic Variants Effects On Breast Cancer Progression
title_full Hemeoxigenase-1 Genetic Variants Effects On Breast Cancer Progression
title_fullStr Hemeoxigenase-1 Genetic Variants Effects On Breast Cancer Progression
title_full_unstemmed Hemeoxigenase-1 Genetic Variants Effects On Breast Cancer Progression
title_sort Hemeoxigenase-1 Genetic Variants Effects On Breast Cancer Progression
dc.creator.none.fl_str_mv Schweitzer, Karen
Alonso, Exequiel Gonzalo
Fernández Chávez, Lucía
Colo, Georgina Pamela
Alonso, Eliana Noelia
Ferronato, María Julia
Fermento, María Eugenia
Curino, Alejandro Carlos
Facchinetti, Maria Marta
author Schweitzer, Karen
author_facet Schweitzer, Karen
Alonso, Exequiel Gonzalo
Fernández Chávez, Lucía
Colo, Georgina Pamela
Alonso, Eliana Noelia
Ferronato, María Julia
Fermento, María Eugenia
Curino, Alejandro Carlos
Facchinetti, Maria Marta
author_role author
author2 Alonso, Exequiel Gonzalo
Fernández Chávez, Lucía
Colo, Georgina Pamela
Alonso, Eliana Noelia
Ferronato, María Julia
Fermento, María Eugenia
Curino, Alejandro Carlos
Facchinetti, Maria Marta
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HO-1
BREAST CANCER
GENETIC VARIANTS
topic HO-1
BREAST CANCER
GENETIC VARIANTS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Hemoxygenase-1 (HO-1) is a microsomal enzyme that catalyzes the degradation of the heme group (canonical role) and can be cleaved at its C-terminal end, followed by translocation to the nucleus, to perform functions at the transcriptional level (non-canonical role). Our laboratory has already demonstrated that HO-1 has antitumoral activity in breast cancer (BC) and that nuclear HO-1 is not enzymatically active. The aim of this work was to study the effect of genetic overexpression of HO-1 variants on cellular processes related to cancer progression, and the molecular mechanisms through which HO-1 modulates the cellular processes investigated. To accomplish this goal, we used the hormone- dependent BC cell line T47D and the triple-negative BC cell lines 4T1 and MDA-MB-231. These cell lines were stably transfected with plasmids overexpressing the HO-1 variants (full-length (FL-HO1), full-length without enzymatic activity (H25A-HO1) and truncated (T-HO1)). We observed significant differences in cell viability between wild-type (WT) cells and cells overexpressing HO-1 variants in the three cell lines evaluated (p<0.05, two-way ANOVA). We found that the WT cell line displays a higher rate of proliferation than those that overexpress FL in the three cell lines analyzed. However, the T-HO1 form behaves differently among cell lines, displaying more proliferative activity in 4T1 and MDA- MB-231 than in T47D cells. The H25A form appear to behave in the same way among cell lines, showing a similar phenotype to WT cells. These results indicate that the overexpression of HO-1 FL seems to display an anti-tumor role. The behavior of the H25A and the T-HO1 variants would indicate that the anti-tumor behavior is the result of both HO-1 enzymatic activity and its nuclear localization. In addition, cell line hormone-dependency would also contribute to the differential effects. Altogether, these results provide evidence of the canonical and non-canonical roles of HO-1 in BC.
Fil: Schweitzer, Karen. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Alonso, Exequiel Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Fernández Chávez, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Colo, Georgina Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Alonso, Eliana Noelia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Ferronato, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Fermento, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Buenos Aires Breast Cancer Symposium
Buenos Aires
Argentina
Universidad de Buenos Aires
description Hemoxygenase-1 (HO-1) is a microsomal enzyme that catalyzes the degradation of the heme group (canonical role) and can be cleaved at its C-terminal end, followed by translocation to the nucleus, to perform functions at the transcriptional level (non-canonical role). Our laboratory has already demonstrated that HO-1 has antitumoral activity in breast cancer (BC) and that nuclear HO-1 is not enzymatically active. The aim of this work was to study the effect of genetic overexpression of HO-1 variants on cellular processes related to cancer progression, and the molecular mechanisms through which HO-1 modulates the cellular processes investigated. To accomplish this goal, we used the hormone- dependent BC cell line T47D and the triple-negative BC cell lines 4T1 and MDA-MB-231. These cell lines were stably transfected with plasmids overexpressing the HO-1 variants (full-length (FL-HO1), full-length without enzymatic activity (H25A-HO1) and truncated (T-HO1)). We observed significant differences in cell viability between wild-type (WT) cells and cells overexpressing HO-1 variants in the three cell lines evaluated (p<0.05, two-way ANOVA). We found that the WT cell line displays a higher rate of proliferation than those that overexpress FL in the three cell lines analyzed. However, the T-HO1 form behaves differently among cell lines, displaying more proliferative activity in 4T1 and MDA- MB-231 than in T47D cells. The H25A form appear to behave in the same way among cell lines, showing a similar phenotype to WT cells. These results indicate that the overexpression of HO-1 FL seems to display an anti-tumor role. The behavior of the H25A and the T-HO1 variants would indicate that the anti-tumor behavior is the result of both HO-1 enzymatic activity and its nuclear localization. In addition, cell line hormone-dependency would also contribute to the differential effects. Altogether, these results provide evidence of the canonical and non-canonical roles of HO-1 in BC.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
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http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/277785
Hemeoxigenase-1 Genetic Variants Effects On Breast Cancer Progression; Buenos Aires Breast Cancer Symposium; Buenos Aires; Argentina; 2024; 98-98
CONICET Digital
CONICET
url http://hdl.handle.net/11336/277785
identifier_str_mv Hemeoxigenase-1 Genetic Variants Effects On Breast Cancer Progression; Buenos Aires Breast Cancer Symposium; Buenos Aires; Argentina; 2024; 98-98
CONICET Digital
CONICET
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language eng
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eu_rights_str_mv openAccess
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dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales
publisher.none.fl_str_mv Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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