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dc.contributor.authorJiménez-García, Manuel-Pedro
dc.contributor.authorLucena-Cacace, Antonio
dc.contributor.authorRobles-Frías, María-José
dc.contributor.authorFerrer, Irene
dc.contributor.authorNarlik-Grassow, Maja
dc.contributor.authorBlanco-Aparicio, Carmen 
dc.contributor.authorCarnero, Amancio
dc.date.accessioned2019-03-14T12:27:17Z
dc.date.available2019-03-14T12:27:17Z
dc.date.issued2017-08-29
dc.identifier.citationOncotarget. 2017 ;8(35):58872-58886es_ES
dc.identifier.issn1949-2553es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/7335
dc.description.abstractThe PIM family of Ser/Thr kinase proteins has been implicated in tumorigenesis at different levels. PIM proteins are overexpressed in several tumor types and have been associated with chemoresistance. However, their role in hormone-dependent female tissues has not been explored, especially in the uterus, breast and ovary. We generated conditional transgenic mice with confined expression of human PIM1 or PIM2 genes in these tissues. We characterized the tumoral response to these genetic alterations corroborating their role as oncogenes since they induce hyperproliferation in all tissues and tumors in mammary gland and uterus. Furthermore, we observed a high degree of inflammatory infiltration in these tissues of transgenic mice accompanied by NFAT and mTOR activation and IL6 expression. Moreover, PIM1/2 were overexpressed in human breast, uterine and ovarian tumors, correlating with inflammatory features and stem cell markers. Our data suggest that PIM1/2 kinase overexpression provoke tissue alterations and a large IL6-dependent inflammatory response that may act synergistically during the process of tumorigenesis. The possible end-point is an increased percentage of cancer stem cells, which may be partly responsible for the therapy resistance found in tumors overexpressing PIM kinases.es_ES
dc.description.sponsorshipThis work was funded by grants from the Spanish Ministry of Economy and Competitivity, Plan Estatal de I+D+I 2013–2016, ISCIII (Fis: PI15/00045) and CIBER de Cáncer (CD16/12/00275), co-funded by FEDER from Regional Development European Funds (European www.impactjournals.com/oncotarget 58885 Oncotarget Union), Consejeria de Ciencia e Innovacion (CTS-1848) and Consejeria de Salud of the Junta de Andalucia (PI- 0096-2014). Especial thanks to the AECC Foundation for also supporting this work. This work has also been made possible by the Fundacion BBVA. The Spanish Ministry of Education (FPU13/00426) funded MPJGes_ES
dc.language.isoenges_ES
dc.publisherImpact Journals es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectPIM kinaseses_ES
dc.subjectConditional transgenic micees_ES
dc.subjectMammary tumorses_ES
dc.subjectOncogenesises_ES
dc.subjectReproductive system tumorses_ES
dc.subject.meshProstate es_ES
dc.subject.meshCHRONIC LYMPHOCYTIC-LEUKEMIAes_ES
dc.subject.meshPIM KINASESes_ES
dc.subject.meshSERINE/THREONINE KINASESes_ES
dc.subject.meshPANCREATIC-CANCERes_ES
dc.subject.meshUp-Regulation es_ES
dc.subject.meshSurvival es_ES
dc.subject.meshGrowth es_ES
dc.subject.meshFamily es_ES
dc.titleInflammation and stem markers association to PIM1/PIM2 kinase-induced tumors in breast and uteruses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID28938604es_ES
dc.format.volume8es_ES
dc.format.number35es_ES
dc.format.page58872-58886es_ES
dc.identifier.doi10.18632/oncotarget.19438es_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderCentro de Investigación Biomedica en Red - CIBER
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.contributor.funderRegional Government of Andalusia (España) 
dc.contributor.funderAsociación Española Contra el Cáncer 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1949-2553es_ES
dc.relation.publisherversionhttps://doi.org/10.18632/oncotarget.19438.es_ES
dc.identifier.journalOncotargetes_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Sección de Biologíaes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI15/00045es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CD16/12/00275es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/CTS-1848es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PI-0096-2014es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/FPU13/00426es_ES
dc.rights.accessRightsopen accesses_ES


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