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dc.contributor.author Bruzzone, Ariana
dc.contributor.author Saulière, Aude
dc.contributor.author Finana, Frédéric
dc.contributor.author Sénard, Jean Michel
dc.contributor.author Luthy, Isabel Alicia
dc.contributor.author Galés, Céline
dc.date.available 2016-07-26T13:53:14Z
dc.date.issued 2014-03-30
dc.identifier.citation 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
dc.identifier.issn 0892-6638
dc.identifier.uri http://hdl.handle.net/11336/6676
dc.description.abstract 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.
dc.format application/pdf
dc.language.iso eng
dc.publisher Federation of American Societies for Experimental Biology
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject MCF-10A
dc.subject HUMAN BREAST CELL LINE
dc.subject EPAC
dc.subject PKA
dc.subject SIGNALING COMPARTMENTALIZATION
dc.subject.classification Bioquímica y Biología Molecular
dc.subject.classification Medicina Básica
dc.subject.classification CIENCIAS MÉDICAS Y DE LA SALUD
dc.title Dosage-dependent regulation of cell prolifration and adhesion through dual beta2-adrenergic receptor/cAMP signals
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2016-06-15T19:08:50Z
dc.identifier.eissn 1530-6860
dc.journal.volume 28
dc.journal.number 3
dc.journal.pagination 1342-1354
dc.journal.pais Estados Unidos
dc.journal.ciudad Bethesda
dc.description.fil Fil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
dc.description.fil Fil: Saulière, Aude. Inserm; Francia
dc.description.fil Fil: Finana, Frédéric . Institut de Recherche Pierre Fabre; Francia
dc.description.fil Fil: Sénard, Jean Michel. Inserm; Francia. Toulouse University Hospital; Francia
dc.description.fil Fil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina
dc.description.fil Fil: Galés, Céline. Inserm; Francia
dc.journal.title Faseb Journal
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/10.1096/fj.13-239285
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://www.fasebj.org/content/28/3/1342.long
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1096/fj.13-239285


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    Articulos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)

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info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)