English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/24497
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:

DC FieldValueLanguage
dc.contributor.authorAcosta, Juan J.-
dc.contributor.authorMuñoz, Raúl M.-
dc.contributor.authorGonzález, Lorena-
dc.contributor.authorSubtil-Rodríguez, Alicia-
dc.contributor.authorDomínguez-Cáceres, Mª Aurora-
dc.contributor.authorGarcía-Martínez, José Manuel-
dc.contributor.authorCalcabrini, Annarica-
dc.contributor.authorLázaro, Icíar-
dc.contributor.authorMartín-Pérez, Jorge-
dc.date.accessioned2010-05-19T12:34:26Z-
dc.date.available2010-05-19T12:34:26Z-
dc.date.issued2003-11-
dc.identifier.citationMolecular Endocrinology 17(11): 2268-2282 (2003)en_US
dc.identifier.issn0888-8809-
dc.identifier.urihttp://hdl.handle.net/10261/24497-
dc.description15 pages, 9 figures.en_US
dc.description.abstractProlactin (PRL) stimulates breast cancer cell proliferation; however, the involvement of PRL-activated signaling molecules in cell proliferation is not fully established. Here we studied the role of c-Src on PRL-stimulated proliferation of T47D and MCF7 breast cancer cells. We initially observed that PRL-dependent activation of focal adhesion kinase (Fak), Erk1/2, and cell proliferation was mediated by c-Src in T47D cells, because expression of a dominant-negative form of c-Src (SrcDM, K295A/Y527F) blocked the PRL-dependent effects. The Src inhibitor PP1 abrogated PRL-dependent in vivo activation of Fak, Erk1/2, p70S6K, and Akt and the proliferation of T47D and MCF7 cells; Janus kinase 2 (Jak2) activation was not affected. However, in vitro, Fak and Jak2 kinases were not directly inhibited by PP1, demonstrating the effect of PP1 on c-Src kinase as an upstream activator of Fak. Expression of Fak mutant Y397F abrogated PRL-dependent activation of Fak, Erk1/2, and thymidine incorporation, but had no effect on p70S6K and Akt kinases. MAPK kinase 1/2 (Mek1/2) inhibitor PD184352 blocked PRL-induced stimulation of Erk1/2 and cell proliferation; however, p70S6K and Akt activation were unaffected. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 abolished cell proliferation and activation of p70S6K and Akt; however, PRL-dependent activation of Erk1/2 was not modified. Moreover, we show that both c-Src/PI3K and c-Src/Fak/Erk1/2 pathways are involved in the up-regulation of c-myc and cyclin d1 expression mediated by PRL. The previous findings suggest the existence of two PRL-dependent signaling cascades, initiated by the c-Src-mediated activation of Fak/Erk1/2 and PI3K pathways that, subsequently, control the expression of c-Myc and cyclin D1 and the proliferation of T47D and MCF7 breast cancer cells.en_US
dc.description.sponsorshipThis work was supported by grants from Ministerio de Ciencia y Tecnologia (PM99-0113 and SAF2003-02188), Comunidad Autónoma de Madrid (08.1/0047/98), and Fondo de Investigaciones Sanitarias (01/1316, 03C03/10). J.J.A. was supported by a fellowship from Fundación Científica de la Asociación Española contra el Cancer; L.G. was supported by a fellowship from Fundación Carolina; and J.M.G.M. was supported by a fellowship from Fondo de Investigaciones Sanitarias. J.M.P. is member of the Spanish Breast Cancer Research Group, which in part supported this research.en_US
dc.format.extent660709 bytes-
dc.format.mimetypeapplication/pdf-
dc.language.isoengen_US
dc.publisherEndocrine Societyen_US
dc.rightsopenAccessen_US
dc.titleSrc mediates prolactin-dependent proliferation of T47D and MCF7 cells via the activation of focal adhesion kinase/Erk1/2 and phosphatidylinositol 3-kinase pathwaysen_US
dc.typeartículoen_US
dc.identifier.doihttp://dx.doi.org/10.1210/me.2002-0422-
dc.description.peerreviewedPeer revieweden_US
dc.relation.publisherversionhttp://dx.doi.org/10.1210/me.2002-0422en_US
Appears in Collections:(IIBM) Artículos
(CIB) Artículos
Files in This Item:
File Description SizeFormat 
Src mediates.pdf645,22 kBAdobe PDFThumbnail
View/Open
Show simple item record
 


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.