Inhibition of p300 suppresses growth of breast cancer. Role of p300 subcellular localization

Autores
Fermento, María Eugenia; Gandini, Norberto Ariel; Salomón, Débora Gisele; Ferronato, María Julia; Vitale, Cristian Alejandro; Arevalo, Julian; Lopez Romero, Alejandro; Nuñez, Myriam Carmen; Jung, Manfred; Facchinetti, Maria Marta; Curino, Alejandro Carlos
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
There is evidence that p300, a transcriptional co-factor and a lysine acetyl-transferase, could play a role both as an oncoprotein and as a tumor suppressor, although little is known regarding its role in breast cancer (BC). First we investigated the role p300 has on BC by performing pharmacological inhibition of p300 acetyl-transferase function and analyzing the effects on cell count, migration and invasion in LM3 murine breast cancer cell line and on tumor progression in a syngeneic murine model. We subsequently studied p300 protein expression in human BC biopsies and evaluated its correlation with clinical and histopathological parameters of the patients. We observed that inhibition of p300 induced apoptosis and reduced migration and invasion in cultured LM3 cells. Furthermore, a significant reduction in tumor burden, number of lung metastases and number of tumors invading the abdominal cavity was observed in a syngeneic tumor model of LM3 following treatment with the p300 inhibitor. This reduction in tumor burden was accompanied by a decrease in the mitotic index and Ki-67 levels and an increase in Bax expression. Moreover, the analysis of p300 expression in human BC samples showed that p300 immunoreactivity is significantly higher in the cancerous tissues than in the non-malignant mammary tissues and in the histologically normal adjacent tissues. Interestingly, p300 was observed in the cytoplasm, and the rate of cytoplasmic p300 was higher in BC than in non-tumor tissues. Importantly, we found that cytoplasmic localization of p300 is associated with a longer overall survival time of the patients. In conclusion, we demonstrated that inhibition of the acetylase function of p300 reduces both cell count and invasion in LM3 cells, and decreases tumor progression in the animal model. In addition, we show that the presence of p300 in the cytoplasm correlates with increased survival of patients suggesting that its nuclear localization is necessary for the pro-tumoral effects.
Fil: Fermento, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Gandini, Norberto Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Salomón, Débora Gisele. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Ferronato, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Vitale, Cristian Alejandro. Universidad Nacional del Sur. Departamento de Química; Argentina
Fil: Arevalo, Julian. Hospital Int. Gral. de Agudos Dr. Jose Penna. Servicio de Patologia; Argentina
Fil: Lopez Romero, Alejandro. Laboratorios IACA. Departamento de Hematología; Argentina
Fil: Nuñez, Myriam Carmen. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Físico Matemática; Argentina
Fil: Jung, Manfred. Albert-Ludwigs University Freiburg. Institute of Pharmaceutical Sciences; Alemania
Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Materia
Breast Cancer
P300
Cell Line
Animal Model
Human Biopsies
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:11336/4520
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/4520
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibition of p300 suppresses growth of breast cancer. Role of p300 subcellular localizationFermento, María EugeniaGandini, Norberto ArielSalomón, Débora GiseleFerronato, María JuliaVitale, Cristian AlejandroArevalo, JulianLopez Romero, AlejandroNuñez, Myriam CarmenJung, ManfredFacchinetti, Maria MartaCurino, Alejandro CarlosBreast CancerP300Cell LineAnimal ModelHuman Biopsieshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3There is evidence that p300, a transcriptional co-factor and a lysine acetyl-transferase, could play a role both as an oncoprotein and as a tumor suppressor, although little is known regarding its role in breast cancer (BC). First we investigated the role p300 has on BC by performing pharmacological inhibition of p300 acetyl-transferase function and analyzing the effects on cell count, migration and invasion in LM3 murine breast cancer cell line and on tumor progression in a syngeneic murine model. We subsequently studied p300 protein expression in human BC biopsies and evaluated its correlation with clinical and histopathological parameters of the patients. We observed that inhibition of p300 induced apoptosis and reduced migration and invasion in cultured LM3 cells. Furthermore, a significant reduction in tumor burden, number of lung metastases and number of tumors invading the abdominal cavity was observed in a syngeneic tumor model of LM3 following treatment with the p300 inhibitor. This reduction in tumor burden was accompanied by a decrease in the mitotic index and Ki-67 levels and an increase in Bax expression. Moreover, the analysis of p300 expression in human BC samples showed that p300 immunoreactivity is significantly higher in the cancerous tissues than in the non-malignant mammary tissues and in the histologically normal adjacent tissues. Interestingly, p300 was observed in the cytoplasm, and the rate of cytoplasmic p300 was higher in BC than in non-tumor tissues. Importantly, we found that cytoplasmic localization of p300 is associated with a longer overall survival time of the patients. In conclusion, we demonstrated that inhibition of the acetylase function of p300 reduces both cell count and invasion in LM3 cells, and decreases tumor progression in the animal model. In addition, we show that the presence of p300 in the cytoplasm correlates with increased survival of patients suggesting that its nuclear localization is necessary for the pro-tumoral effects.Fil: Fermento, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Gandini, Norberto Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Salomón, Débora Gisele. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Ferronato, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Vitale, Cristian Alejandro. Universidad Nacional del Sur. Departamento de Química; ArgentinaFil: Arevalo, Julian. Hospital Int. Gral. de Agudos Dr. Jose Penna. Servicio de Patologia; ArgentinaFil: Lopez Romero, Alejandro. Laboratorios IACA. Departamento de Hematología; ArgentinaFil: Nuñez, Myriam Carmen. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Físico Matemática; ArgentinaFil: Jung, Manfred. Albert-Ludwigs University Freiburg. Institute of Pharmaceutical Sciences; AlemaniaFil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaAcademic Press Inc Elsevier Science2014-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/4520Fermento, María Eugenia; Gandini, Norberto Ariel; Salomón, Débora Gisele; Ferronato, María Julia; Vitale, Cristian Alejandro; et al.; Inhibition of p300 suppresses growth of breast cancer. Role of p300 subcellular localization; Academic Press Inc Elsevier Science; Experimental And Molecular Pathology.; 97; 9-2014; 411-4240014-4800enginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pubmed/25240203info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yexmp.2014.09.019info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:05:29Zoai:ri.conicet.gov.ar:11336/4520instacron: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:34982025-09-10 13:05:29.835CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibition of p300 suppresses growth of breast cancer. Role of p300 subcellular localization
title Inhibition of p300 suppresses growth of breast cancer. Role of p300 subcellular localization
spellingShingle Inhibition of p300 suppresses growth of breast cancer. Role of p300 subcellular localization
Fermento, María Eugenia
Breast Cancer
P300
Cell Line
Animal Model
Human Biopsies
title_short Inhibition of p300 suppresses growth of breast cancer. Role of p300 subcellular localization
title_full Inhibition of p300 suppresses growth of breast cancer. Role of p300 subcellular localization
title_fullStr Inhibition of p300 suppresses growth of breast cancer. Role of p300 subcellular localization
title_full_unstemmed Inhibition of p300 suppresses growth of breast cancer. Role of p300 subcellular localization
title_sort Inhibition of p300 suppresses growth of breast cancer. Role of p300 subcellular localization
dc.creator.none.fl_str_mv Fermento, María Eugenia
Gandini, Norberto Ariel
Salomón, Débora Gisele
Ferronato, María Julia
Vitale, Cristian Alejandro
Arevalo, Julian
Lopez Romero, Alejandro
Nuñez, Myriam Carmen
Jung, Manfred
Facchinetti, Maria Marta
Curino, Alejandro Carlos
author Fermento, María Eugenia
author_facet Fermento, María Eugenia
Gandini, Norberto Ariel
Salomón, Débora Gisele
Ferronato, María Julia
Vitale, Cristian Alejandro
Arevalo, Julian
Lopez Romero, Alejandro
Nuñez, Myriam Carmen
Jung, Manfred
Facchinetti, Maria Marta
Curino, Alejandro Carlos
author_role author
author2 Gandini, Norberto Ariel
Salomón, Débora Gisele
Ferronato, María Julia
Vitale, Cristian Alejandro
Arevalo, Julian
Lopez Romero, Alejandro
Nuñez, Myriam Carmen
Jung, Manfred
Facchinetti, Maria Marta
Curino, Alejandro Carlos
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Breast Cancer
P300
Cell Line
Animal Model
Human Biopsies
topic Breast Cancer
P300
Cell Line
Animal Model
Human Biopsies
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv There is evidence that p300, a transcriptional co-factor and a lysine acetyl-transferase, could play a role both as an oncoprotein and as a tumor suppressor, although little is known regarding its role in breast cancer (BC). First we investigated the role p300 has on BC by performing pharmacological inhibition of p300 acetyl-transferase function and analyzing the effects on cell count, migration and invasion in LM3 murine breast cancer cell line and on tumor progression in a syngeneic murine model. We subsequently studied p300 protein expression in human BC biopsies and evaluated its correlation with clinical and histopathological parameters of the patients. We observed that inhibition of p300 induced apoptosis and reduced migration and invasion in cultured LM3 cells. Furthermore, a significant reduction in tumor burden, number of lung metastases and number of tumors invading the abdominal cavity was observed in a syngeneic tumor model of LM3 following treatment with the p300 inhibitor. This reduction in tumor burden was accompanied by a decrease in the mitotic index and Ki-67 levels and an increase in Bax expression. Moreover, the analysis of p300 expression in human BC samples showed that p300 immunoreactivity is significantly higher in the cancerous tissues than in the non-malignant mammary tissues and in the histologically normal adjacent tissues. Interestingly, p300 was observed in the cytoplasm, and the rate of cytoplasmic p300 was higher in BC than in non-tumor tissues. Importantly, we found that cytoplasmic localization of p300 is associated with a longer overall survival time of the patients. In conclusion, we demonstrated that inhibition of the acetylase function of p300 reduces both cell count and invasion in LM3 cells, and decreases tumor progression in the animal model. In addition, we show that the presence of p300 in the cytoplasm correlates with increased survival of patients suggesting that its nuclear localization is necessary for the pro-tumoral effects.
Fil: Fermento, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Gandini, Norberto Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Salomón, Débora Gisele. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Ferronato, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Vitale, Cristian Alejandro. Universidad Nacional del Sur. Departamento de Química; Argentina
Fil: Arevalo, Julian. Hospital Int. Gral. de Agudos Dr. Jose Penna. Servicio de Patologia; Argentina
Fil: Lopez Romero, Alejandro. Laboratorios IACA. Departamento de Hematología; Argentina
Fil: Nuñez, Myriam Carmen. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Físico Matemática; Argentina
Fil: Jung, Manfred. Albert-Ludwigs University Freiburg. Institute of Pharmaceutical Sciences; Alemania
Fil: Facchinetti, Maria Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Curino, Alejandro Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
description There is evidence that p300, a transcriptional co-factor and a lysine acetyl-transferase, could play a role both as an oncoprotein and as a tumor suppressor, although little is known regarding its role in breast cancer (BC). First we investigated the role p300 has on BC by performing pharmacological inhibition of p300 acetyl-transferase function and analyzing the effects on cell count, migration and invasion in LM3 murine breast cancer cell line and on tumor progression in a syngeneic murine model. We subsequently studied p300 protein expression in human BC biopsies and evaluated its correlation with clinical and histopathological parameters of the patients. We observed that inhibition of p300 induced apoptosis and reduced migration and invasion in cultured LM3 cells. Furthermore, a significant reduction in tumor burden, number of lung metastases and number of tumors invading the abdominal cavity was observed in a syngeneic tumor model of LM3 following treatment with the p300 inhibitor. This reduction in tumor burden was accompanied by a decrease in the mitotic index and Ki-67 levels and an increase in Bax expression. Moreover, the analysis of p300 expression in human BC samples showed that p300 immunoreactivity is significantly higher in the cancerous tissues than in the non-malignant mammary tissues and in the histologically normal adjacent tissues. Interestingly, p300 was observed in the cytoplasm, and the rate of cytoplasmic p300 was higher in BC than in non-tumor tissues. Importantly, we found that cytoplasmic localization of p300 is associated with a longer overall survival time of the patients. In conclusion, we demonstrated that inhibition of the acetylase function of p300 reduces both cell count and invasion in LM3 cells, and decreases tumor progression in the animal model. In addition, we show that the presence of p300 in the cytoplasm correlates with increased survival of patients suggesting that its nuclear localization is necessary for the pro-tumoral 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/11336/4520
Fermento, María Eugenia; Gandini, Norberto Ariel; Salomón, Débora Gisele; Ferronato, María Julia; Vitale, Cristian Alejandro; et al.; Inhibition of p300 suppresses growth of breast cancer. Role of p300 subcellular localization; Academic Press Inc Elsevier Science; Experimental And Molecular Pathology.; 97; 9-2014; 411-424
0014-4800
url http://hdl.handle.net/11336/4520
identifier_str_mv Fermento, María Eugenia; Gandini, Norberto Ariel; Salomón, Débora Gisele; Ferronato, María Julia; Vitale, Cristian Alejandro; et al.; Inhibition of p300 suppresses growth of breast cancer. Role of p300 subcellular localization; Academic Press Inc Elsevier Science; Experimental And Molecular Pathology.; 97; 9-2014; 411-424
0014-4800
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pubmed/25240203
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.yexmp.2014.09.019
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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 12.993085

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