Adrenergic receptors in breast cancer: differential effects of alpha2A and 2C-adrenergic receptor expression on tamoxifen sensitivity in stably transfected luminal MCF-7 cells

Autores
Aparicio, Evangelina; Rivero, Ezequiel Mariano; Bruque, Carlos David; Rodriguez, Maria Sol; Bruzzone, Ariana; Perez, Cecilia; Luthy, Isabel Alicia
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Breast cancer is the most frequently diagnosed and leading cause of cancer death among women worldwide. Epinephrine and norepinephrine, released during stress, bind to 9 different adrenoceptors. Our group has already described (SAIC 2015, poster 660) by in silico analysis in a great database that patients with high expression of Alpha2A- adrenoceptors (A2A-AR) have better disease-free survival than those with lower expression, mainly in luminal tamoxifen-treated ones. Contrarily, a high expression of Alpha2C-AR was associated with worse outcome in luminal B but not in luminal A patients. The aim of the present work was to study the sensibility of tamoxifen on A2A or A2C-AR-overexpressing cells. The human luminal breast cancer MCF-7 cells were stably transfected with A2A or A2C-AR or the empty vector. The expression of A2-AR and Estrogen Receptor Alpha (ER) was measured by RT-qPCR, the sensitivity to tamoxifen by tritiated thymidine incorporation and ER, progesterone receptor and pERK relative to ERK, by Western Blot. They were all performed in the absence of adrenergic stimulation because catecholamines released during stress bind to all receptors and no specific ligand for individual A2-AR exists yet. We successfully over expressed alpha2A and alpha2C on MCF-7 cells: 65 (A2A) and 28 % (A2C) increase compared with empty vector (pCDNA, p<0.05 and p<0.01, respectively). When analyzing the sensitivity to tamoxifen treatment, the A2A cells exhibited an EC50 of 2.867e-10 vs. 4.250 e-10 of pCDNA, p<0.01; while A2C of 1.202e-9, p<0.001.This was accompanied by a decrease in both cases of ER levels measured by RT-qPCR, p<0.05 and WB. A2A cells also showed diminished cell proliferation (p<0.01) in the absence of any stimulation when compared with pCDNA and A2C. We suggest that the increase of tamoxifen sensitivity in A2A cells could be due to the combined effect of inhibiting ER expression and cell proliferation.
Fil: Aparicio, Evangelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Rivero, Ezequiel Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bruque, Carlos David. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rodriguez, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bruzzone, Ariana. 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: Perez, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Reunión Anual de Sociedades de Biociencia
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
The Histochemical Society
Materia
BREAST
CANCER
ADRENERGIC
RECEPTOR
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:11336/157900
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/157900
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Adrenergic receptors in breast cancer: differential effects of alpha2A and 2C-adrenergic receptor expression on tamoxifen sensitivity in stably transfected luminal MCF-7 cellsAparicio, EvangelinaRivero, Ezequiel MarianoBruque, Carlos DavidRodriguez, Maria SolBruzzone, ArianaPerez, CeciliaLuthy, Isabel AliciaBREASTCANCERADRENERGICRECEPTORhttps://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3Breast cancer is the most frequently diagnosed and leading cause of cancer death among women worldwide. Epinephrine and norepinephrine, released during stress, bind to 9 different adrenoceptors. Our group has already described (SAIC 2015, poster 660) by in silico analysis in a great database that patients with high expression of Alpha2A- adrenoceptors (A2A-AR) have better disease-free survival than those with lower expression, mainly in luminal tamoxifen-treated ones. Contrarily, a high expression of Alpha2C-AR was associated with worse outcome in luminal B but not in luminal A patients. The aim of the present work was to study the sensibility of tamoxifen on A2A or A2C-AR-overexpressing cells. The human luminal breast cancer MCF-7 cells were stably transfected with A2A or A2C-AR or the empty vector. The expression of A2-AR and Estrogen Receptor Alpha (ER) was measured by RT-qPCR, the sensitivity to tamoxifen by tritiated thymidine incorporation and ER, progesterone receptor and pERK relative to ERK, by Western Blot. They were all performed in the absence of adrenergic stimulation because catecholamines released during stress bind to all receptors and no specific ligand for individual A2-AR exists yet. We successfully over expressed alpha2A and alpha2C on MCF-7 cells: 65 (A2A) and 28 % (A2C) increase compared with empty vector (pCDNA, p<0.05 and p<0.01, respectively). When analyzing the sensitivity to tamoxifen treatment, the A2A cells exhibited an EC50 of 2.867e-10 vs. 4.250 e-10 of pCDNA, p<0.01; while A2C of 1.202e-9, p<0.001.This was accompanied by a decrease in both cases of ER levels measured by RT-qPCR, p<0.05 and WB. A2A cells also showed diminished cell proliferation (p<0.01) in the absence of any stimulation when compared with pCDNA and A2C. We suggest that the increase of tamoxifen sensitivity in A2A cells could be due to the combined effect of inhibiting ER expression and cell proliferation.Fil: Aparicio, Evangelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rivero, Ezequiel Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bruque, Carlos David. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodriguez, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bruzzone, Ariana. 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: Perez, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaReunión Anual de Sociedades de BiocienciaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioThe Histochemical SocietyFundación Revista Medicina2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/157900Adrenergic receptors in breast cancer: differential effects of alpha2A and 2C-adrenergic receptor expression on tamoxifen sensitivity in stably transfected luminal MCF-7 cells; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 305-3050025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:39:20Zoai:ri.conicet.gov.ar:11336/157900instacron: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:34982025-09-29 09:39:20.308CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Adrenergic receptors in breast cancer: differential effects of alpha2A and 2C-adrenergic receptor expression on tamoxifen sensitivity in stably transfected luminal MCF-7 cells
title Adrenergic receptors in breast cancer: differential effects of alpha2A and 2C-adrenergic receptor expression on tamoxifen sensitivity in stably transfected luminal MCF-7 cells
spellingShingle Adrenergic receptors in breast cancer: differential effects of alpha2A and 2C-adrenergic receptor expression on tamoxifen sensitivity in stably transfected luminal MCF-7 cells
Aparicio, Evangelina
BREAST
CANCER
ADRENERGIC
RECEPTOR
title_short Adrenergic receptors in breast cancer: differential effects of alpha2A and 2C-adrenergic receptor expression on tamoxifen sensitivity in stably transfected luminal MCF-7 cells
title_full Adrenergic receptors in breast cancer: differential effects of alpha2A and 2C-adrenergic receptor expression on tamoxifen sensitivity in stably transfected luminal MCF-7 cells
title_fullStr Adrenergic receptors in breast cancer: differential effects of alpha2A and 2C-adrenergic receptor expression on tamoxifen sensitivity in stably transfected luminal MCF-7 cells
title_full_unstemmed Adrenergic receptors in breast cancer: differential effects of alpha2A and 2C-adrenergic receptor expression on tamoxifen sensitivity in stably transfected luminal MCF-7 cells
title_sort Adrenergic receptors in breast cancer: differential effects of alpha2A and 2C-adrenergic receptor expression on tamoxifen sensitivity in stably transfected luminal MCF-7 cells
dc.creator.none.fl_str_mv Aparicio, Evangelina
Rivero, Ezequiel Mariano
Bruque, Carlos David
Rodriguez, Maria Sol
Bruzzone, Ariana
Perez, Cecilia
Luthy, Isabel Alicia
author Aparicio, Evangelina
author_facet Aparicio, Evangelina
Rivero, Ezequiel Mariano
Bruque, Carlos David
Rodriguez, Maria Sol
Bruzzone, Ariana
Perez, Cecilia
Luthy, Isabel Alicia
author_role author
author2 Rivero, Ezequiel Mariano
Bruque, Carlos David
Rodriguez, Maria Sol
Bruzzone, Ariana
Perez, Cecilia
Luthy, Isabel Alicia
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv BREAST
CANCER
ADRENERGIC
RECEPTOR
topic BREAST
CANCER
ADRENERGIC
RECEPTOR
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Breast cancer is the most frequently diagnosed and leading cause of cancer death among women worldwide. Epinephrine and norepinephrine, released during stress, bind to 9 different adrenoceptors. Our group has already described (SAIC 2015, poster 660) by in silico analysis in a great database that patients with high expression of Alpha2A- adrenoceptors (A2A-AR) have better disease-free survival than those with lower expression, mainly in luminal tamoxifen-treated ones. Contrarily, a high expression of Alpha2C-AR was associated with worse outcome in luminal B but not in luminal A patients. The aim of the present work was to study the sensibility of tamoxifen on A2A or A2C-AR-overexpressing cells. The human luminal breast cancer MCF-7 cells were stably transfected with A2A or A2C-AR or the empty vector. The expression of A2-AR and Estrogen Receptor Alpha (ER) was measured by RT-qPCR, the sensitivity to tamoxifen by tritiated thymidine incorporation and ER, progesterone receptor and pERK relative to ERK, by Western Blot. They were all performed in the absence of adrenergic stimulation because catecholamines released during stress bind to all receptors and no specific ligand for individual A2-AR exists yet. We successfully over expressed alpha2A and alpha2C on MCF-7 cells: 65 (A2A) and 28 % (A2C) increase compared with empty vector (pCDNA, p<0.05 and p<0.01, respectively). When analyzing the sensitivity to tamoxifen treatment, the A2A cells exhibited an EC50 of 2.867e-10 vs. 4.250 e-10 of pCDNA, p<0.01; while A2C of 1.202e-9, p<0.001.This was accompanied by a decrease in both cases of ER levels measured by RT-qPCR, p<0.05 and WB. A2A cells also showed diminished cell proliferation (p<0.01) in the absence of any stimulation when compared with pCDNA and A2C. We suggest that the increase of tamoxifen sensitivity in A2A cells could be due to the combined effect of inhibiting ER expression and cell proliferation.
Fil: Aparicio, Evangelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Rivero, Ezequiel Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bruque, Carlos David. Administración Nacional de Laboratorio e Institutos de Salud "Dr. Carlos G. Malbrán". Instituto Nacional de Epidemiologia. Departamento de Investigación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Rodriguez, Maria Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bruzzone, Ariana. 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: Perez, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Reunión Anual de Sociedades de Biociencia
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Nanomedicinas
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
The Histochemical Society
description Breast cancer is the most frequently diagnosed and leading cause of cancer death among women worldwide. Epinephrine and norepinephrine, released during stress, bind to 9 different adrenoceptors. Our group has already described (SAIC 2015, poster 660) by in silico analysis in a great database that patients with high expression of Alpha2A- adrenoceptors (A2A-AR) have better disease-free survival than those with lower expression, mainly in luminal tamoxifen-treated ones. Contrarily, a high expression of Alpha2C-AR was associated with worse outcome in luminal B but not in luminal A patients. The aim of the present work was to study the sensibility of tamoxifen on A2A or A2C-AR-overexpressing cells. The human luminal breast cancer MCF-7 cells were stably transfected with A2A or A2C-AR or the empty vector. The expression of A2-AR and Estrogen Receptor Alpha (ER) was measured by RT-qPCR, the sensitivity to tamoxifen by tritiated thymidine incorporation and ER, progesterone receptor and pERK relative to ERK, by Western Blot. They were all performed in the absence of adrenergic stimulation because catecholamines released during stress bind to all receptors and no specific ligand for individual A2-AR exists yet. We successfully over expressed alpha2A and alpha2C on MCF-7 cells: 65 (A2A) and 28 % (A2C) increase compared with empty vector (pCDNA, p<0.05 and p<0.01, respectively). When analyzing the sensitivity to tamoxifen treatment, the A2A cells exhibited an EC50 of 2.867e-10 vs. 4.250 e-10 of pCDNA, p<0.01; while A2C of 1.202e-9, p<0.001.This was accompanied by a decrease in both cases of ER levels measured by RT-qPCR, p<0.05 and WB. A2A cells also showed diminished cell proliferation (p<0.01) in the absence of any stimulation when compared with pCDNA and A2C. We suggest that the increase of tamoxifen sensitivity in A2A cells could be due to the combined effect of inhibiting ER expression and cell proliferation.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
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/11336/157900
Adrenergic receptors in breast cancer: differential effects of alpha2A and 2C-adrenergic receptor expression on tamoxifen sensitivity in stably transfected luminal MCF-7 cells; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 305-305
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/157900
identifier_str_mv Adrenergic receptors in breast cancer: differential effects of alpha2A and 2C-adrenergic receptor expression on tamoxifen sensitivity in stably transfected luminal MCF-7 cells; Reunión Anual de Sociedades de Biociencia; Mar del Plata; Argentina; 2019; 305-305
0025-7680
1669-9106
CONICET Digital
CONICET
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language eng
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dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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