Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals

Autores
Bruzzone, Ariana; Saulière, Aude; Finana, Frédéric; Sénard, Jean Michel; Luthy, Isabel Alicia; Galés, Céline
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The role of Beta-adrenergic receptors (B-ARs) remains controversial in normal and tumor breast. Herein we explore the cAMP signaling involved in B-AR-dependent control of proliferation and adhesion of nontumor human breast cell line MCF-10A. Low concentrations of a B-agonist, isoproterenol (ISO), promote cell adhesion (87.5% cells remaining adherent to the plastic dishes following specific detachment vs. 35.0% in control, P 0.001), while increasing concentrations further engages an additional 36% inhibition of Erk1/2 phosphorylation (p-Erk1/2) -dependent cell proliferation (P 0.01). Isoproterenol dose response on cell adhesion was fitted to a 2-site curve (EC50(1): 16.5 +/-11.5 fM, EC50(2): 4.08 +/- 3.09 nM), while ISO significantly inhibited p-Erk1/2 according to a 1-site model (EC50: 0.25 +/- 0.13 nM). Using B-AR-selective agonist/antagonists and cAMP analogs/inhibitors, we identified a dosage-dependent signaling in which low ISO concentrations target a B2-AR population localized in raft microdomains and stimulate a Gs/cAMP/Epac/adhesion-signaling module, while higher concentrations engage a concomitant activation of another B2-AR population outside rafts and inhibit the proliferation by a Gs/cAMP/PKA-dependent signaling module. Our data provide a new molecular basis for the dose-dependent switch of B-AR signaling. This study also sheds light on a new cAMP pathway core mechanism with a single receptor triggering dual cAMP signaling controlled by PKA or Epac but with different cellular outputs.
Fil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Saulière, Aude. Inserm; Francia
Fil: Finana, Frédéric . Institut de Recherche Pierre Fabre; Francia
Fil: Sénard, Jean Michel. Inserm; Francia. Toulouse University Hospital; Francia
Fil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Galés, Céline. Inserm; Francia
Materia
Mcf-10a
Human Breast Cell Line
Epac
Pka
Signaling Compartmentalization
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:11336/6676
Acceder
id CONICETDig_9f35871ff1648bdbad5f236cddbaef94
oai_identifier_str oai:ri.conicet.gov.ar:11336/6676
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signalsBruzzone, ArianaSaulière, AudeFinana, Frédéric Sénard, Jean MichelLuthy, Isabel AliciaGalés, CélineMcf-10aHuman Breast Cell LineEpacPkaSignaling Compartmentalizationhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The role of Beta-adrenergic receptors (B-ARs) remains controversial in normal and tumor breast. Herein we explore the cAMP signaling involved in B-AR-dependent control of proliferation and adhesion of nontumor human breast cell line MCF-10A. Low concentrations of a B-agonist, isoproterenol (ISO), promote cell adhesion (87.5% cells remaining adherent to the plastic dishes following specific detachment vs. 35.0% in control, P 0.001), while increasing concentrations further engages an additional 36% inhibition of Erk1/2 phosphorylation (p-Erk1/2) -dependent cell proliferation (P 0.01). Isoproterenol dose response on cell adhesion was fitted to a 2-site curve (EC50(1): 16.5 +/-11.5 fM, EC50(2): 4.08 +/- 3.09 nM), while ISO significantly inhibited p-Erk1/2 according to a 1-site model (EC50: 0.25 +/- 0.13 nM). Using B-AR-selective agonist/antagonists and cAMP analogs/inhibitors, we identified a dosage-dependent signaling in which low ISO concentrations target a B2-AR population localized in raft microdomains and stimulate a Gs/cAMP/Epac/adhesion-signaling module, while higher concentrations engage a concomitant activation of another B2-AR population outside rafts and inhibit the proliferation by a Gs/cAMP/PKA-dependent signaling module. Our data provide a new molecular basis for the dose-dependent switch of B-AR signaling. This study also sheds light on a new cAMP pathway core mechanism with a single receptor triggering dual cAMP signaling controlled by PKA or Epac but with different cellular outputs.Fil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Saulière, Aude. Inserm; FranciaFil: Finana, Frédéric . Institut de Recherche Pierre Fabre; FranciaFil: Sénard, Jean Michel. Inserm; Francia. Toulouse University Hospital; FranciaFil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Galés, Céline. Inserm; FranciaFederation of American Societies for Experimental Biology2014-03-30info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/6676Bruzzone, Ariana; Saulière, Aude; Finana, Frédéric ; Sénard, Jean Michel; Luthy, Isabel Alicia; et al.; Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals; Federation of American Societies for Experimental Biology; Faseb Journal; 28; 3; 30-3-2014; 1342-13540892-66381530-6860enginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/url/http://www.fasebj.org/content/28/3/1342.longinfo:eu-repo/semantics/altIdentifier/doi/10.1096/fj.13-239285info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:26:58Zoai:ri.conicet.gov.ar:11336/6676instacron: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:34982025-10-15 14:26:58.484CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals
title Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals
spellingShingle Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals
Bruzzone, Ariana
Mcf-10a
Human Breast Cell Line
Epac
Pka
Signaling Compartmentalization
title_short Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals
title_full Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals
title_fullStr Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals
title_full_unstemmed Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals
title_sort Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals
dc.creator.none.fl_str_mv Bruzzone, Ariana
Saulière, Aude
Finana, Frédéric
Sénard, Jean Michel
Luthy, Isabel Alicia
Galés, Céline
author Bruzzone, Ariana
author_facet Bruzzone, Ariana
Saulière, Aude
Finana, Frédéric
Sénard, Jean Michel
Luthy, Isabel Alicia
Galés, Céline
author_role author
author2 Saulière, Aude
Finana, Frédéric
Sénard, Jean Michel
Luthy, Isabel Alicia
Galés, Céline
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Mcf-10a
Human Breast Cell Line
Epac
Pka
Signaling Compartmentalization
topic Mcf-10a
Human Breast Cell Line
Epac
Pka
Signaling Compartmentalization
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 role of Beta-adrenergic receptors (B-ARs) remains controversial in normal and tumor breast. Herein we explore the cAMP signaling involved in B-AR-dependent control of proliferation and adhesion of nontumor human breast cell line MCF-10A. Low concentrations of a B-agonist, isoproterenol (ISO), promote cell adhesion (87.5% cells remaining adherent to the plastic dishes following specific detachment vs. 35.0% in control, P 0.001), while increasing concentrations further engages an additional 36% inhibition of Erk1/2 phosphorylation (p-Erk1/2) -dependent cell proliferation (P 0.01). Isoproterenol dose response on cell adhesion was fitted to a 2-site curve (EC50(1): 16.5 +/-11.5 fM, EC50(2): 4.08 +/- 3.09 nM), while ISO significantly inhibited p-Erk1/2 according to a 1-site model (EC50: 0.25 +/- 0.13 nM). Using B-AR-selective agonist/antagonists and cAMP analogs/inhibitors, we identified a dosage-dependent signaling in which low ISO concentrations target a B2-AR population localized in raft microdomains and stimulate a Gs/cAMP/Epac/adhesion-signaling module, while higher concentrations engage a concomitant activation of another B2-AR population outside rafts and inhibit the proliferation by a Gs/cAMP/PKA-dependent signaling module. Our data provide a new molecular basis for the dose-dependent switch of B-AR signaling. This study also sheds light on a new cAMP pathway core mechanism with a single receptor triggering dual cAMP signaling controlled by PKA or Epac but with different cellular outputs.
Fil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Saulière, Aude. Inserm; Francia
Fil: Finana, Frédéric . Institut de Recherche Pierre Fabre; Francia
Fil: Sénard, Jean Michel. Inserm; Francia. Toulouse University Hospital; Francia
Fil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
Fil: Galés, Céline. Inserm; Francia
description The role of Beta-adrenergic receptors (B-ARs) remains controversial in normal and tumor breast. Herein we explore the cAMP signaling involved in B-AR-dependent control of proliferation and adhesion of nontumor human breast cell line MCF-10A. Low concentrations of a B-agonist, isoproterenol (ISO), promote cell adhesion (87.5% cells remaining adherent to the plastic dishes following specific detachment vs. 35.0% in control, P 0.001), while increasing concentrations further engages an additional 36% inhibition of Erk1/2 phosphorylation (p-Erk1/2) -dependent cell proliferation (P 0.01). Isoproterenol dose response on cell adhesion was fitted to a 2-site curve (EC50(1): 16.5 +/-11.5 fM, EC50(2): 4.08 +/- 3.09 nM), while ISO significantly inhibited p-Erk1/2 according to a 1-site model (EC50: 0.25 +/- 0.13 nM). Using B-AR-selective agonist/antagonists and cAMP analogs/inhibitors, we identified a dosage-dependent signaling in which low ISO concentrations target a B2-AR population localized in raft microdomains and stimulate a Gs/cAMP/Epac/adhesion-signaling module, while higher concentrations engage a concomitant activation of another B2-AR population outside rafts and inhibit the proliferation by a Gs/cAMP/PKA-dependent signaling module. Our data provide a new molecular basis for the dose-dependent switch of B-AR signaling. This study also sheds light on a new cAMP pathway core mechanism with a single receptor triggering dual cAMP signaling controlled by PKA or Epac but with different cellular outputs.
publishDate 2014
dc.date.none.fl_str_mv 2014-03-30
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/11336/6676
Bruzzone, Ariana; Saulière, Aude; Finana, Frédéric ; Sénard, Jean Michel; Luthy, Isabel Alicia; et al.; Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals; Federation of American Societies for Experimental Biology; Faseb Journal; 28; 3; 30-3-2014; 1342-1354
0892-6638
1530-6860
url http://hdl.handle.net/11336/6676
identifier_str_mv Bruzzone, Ariana; Saulière, Aude; Finana, Frédéric ; Sénard, Jean Michel; Luthy, Isabel Alicia; et al.; Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals; Federation of American Societies for Experimental Biology; Faseb Journal; 28; 3; 30-3-2014; 1342-1354
0892-6638
1530-6860
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.fasebj.org/content/28/3/1342.long
info:eu-repo/semantics/altIdentifier/doi/10.1096/fj.13-239285
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
publisher.none.fl_str_mv Federation of American Societies for Experimental Biology
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
_version_ 1846082720947503104
score 13.22299

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