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dc.contributor.authorCastillo, Sonia-
dc.contributor.authorHontecillas-Prieto, Lourdes-
dc.contributor.authorBlanco-Gómez, Adrián-
dc.contributor.authorSáez-Freire, María del Mar-
dc.contributor.authorGarcía-Cenador, Begoña-
dc.contributor.authorGarcía-Criado, Francisco Javier-
dc.contributor.authorPérez-Andrés, Martin-
dc.contributor.authorOrfao, Alberto-
dc.contributor.authorCañamero, Marta-
dc.contributor.authorMao, Jian-Hua-
dc.contributor.authorGridley, Thomas-
dc.contributor.authorCastellanos-Martín, Andrés-
dc.contributor.authorPérez-Losada, J.-
dc.date.accessioned2016-08-22T08:52:30Z-
dc.date.available2016-08-22T08:52:30Z-
dc.date.issued2015-
dc.identifierdoi: 10.1038/onc.2015.224-
dc.identifiere-issn: 1476-5594-
dc.identifierissn: 0950-9232-
dc.identifier.citationOncogene 34(36): 4777-4790 (2015)-
dc.identifier.urihttp://hdl.handle.net/10261/135721-
dc.descriptionPMCID: PMC4560637-
dc.description.abstractBreast cancer is a major cause of mortality in women. The transcription factor SNAI2 has been implicated in the pathogenesis of several types of cancer, including breast cancer of basal origin. Here we show that SNAI2 is also important in the development of breast cancer of luminal origin in MMTV-ErbB2 mice. SNAI2 deficiency leads to longer latency and fewer luminal tumors, both of these being characteristics of pretumoral origin. These effects were associated with reduced proliferation and a decreased ability to generate mammospheres in normal mammary glands. However, the capacity to metastasize was not modified. Under conditions of increased ERBB2 oncogenic activity after pregnancy plus SNAI2 deficiency, both pretumoral defects - latency and tumor load - were compensated. However, the incidence of lung metastases was dramatically reduced. Furthermore, SNAI2 was required for proper postlactational involution of the breast. At 3 days post lactational involution, the mammary glands of Snai2-deficient mice exhibited lower levels of pSTAT3 and higher levels of pAKT1, resulting in decreased apoptosis. Abundant noninvoluted ducts were still present at 30 days post lactation, with a greater number of residual ERBB2+ cells. These results suggest that this defect in involution leads to an increase in the number of susceptible target cells for transformation, to the recovery of the capacity to generate mammospheres and to an increase in the number of tumors. Our work demonstrates the participation of SNAI2 in the pathogenesis of luminal breast cancer, and reveals an unexpected connection between the processes of postlactational involution and breast tumorigenesis in Snai2-null mutant mice.-
dc.description.sponsorshipJPL was partially supported by FEDER and MICINN (PLE2009-119, SAF2014-56989-R), Instituto de Salud Carlos III (PI07/0057, PI10/00328, PIE14/00066), Junta de Castilla y León (SAN673/SA26/08, SAN126/SA66/09, SA078A09, CSI034U13), the “Fundación Eugenio Rodríguez Pascual”, the “Fundación Inbiomed” (Instituto Oncológico Obra Social de la Caja Guipozcoa-San Sebastian, Kutxa), and the “Fundación Sandra Ibarra de Solidaridad frente al Cáncer”. AC was supported by FIS (PI07/0057) and MICINN (PLE2009-119). SCLL was funded by a JAEdoc Fellowship (CSIC)/FSE. MMSF and ABG are funded by fellowships from the Junta de Castilla y Leon. JHM was supported by the National Institutes of Health, a National Cancer Institute grant (R01 CA116481), and the Low-Dose Scientific Focus Area, Office of Biological & Environmental Research, US Department of Energy (DE-AC02-05CH11231).-
dc.publisherNature Publishing Group-
dc.relationMINECO/ICTI2013-2016/SAF2014-56989-R-
dc.relation.isversionofPostprint-
dc.rightsopenAccess-
dc.subjectPost-lactational involution-
dc.subjectSNAI2-
dc.subjectLuminal breast cancer-
dc.subjectERBB2-
dc.titleA new role of SNAI2 in postlactational involution of the mammary gland links it to luminal breast cancer development-
dc.typeArtículo-
dc.identifier.doi10.1038/onc.2015.224-
dc.relation.publisherversionhttp://dx.doi.org/10.1038/onc.2015.224-
dc.date.updated2016-08-22T08:52:31Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.contributor.funderNational Cancer Institute (US)-
dc.contributor.funderDepartment of Energy (US)-
dc.contributor.funderNational Institutes of Health (US)-
dc.contributor.funderMinisterio de Ciencia e Innovación (España)-
dc.contributor.funderEuropean Commission-
dc.contributor.funderConsejo Superior de Investigaciones Científicas (España)-
dc.contributor.funderInstituto de Salud Carlos III-
dc.contributor.funderFundación Sandra Ibarra - Solidaridad Frente al Cáncer-
dc.contributor.funderObra Social Kutxa-
dc.contributor.funderJunta de Castilla y León-
dc.contributor.funderFundación Eugenio Rodríguez Pascual-
dc.relation.csic-
dc.identifier.funderhttp://dx.doi.org/10.13039/100000002es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004837es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003339es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100007649es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100008055es_ES
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