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dc.contributor.authorMuñoz-Lorente, Miguel A
dc.contributor.authorMartinez Rodriguez , Paula 
dc.contributor.authorTejera, Agueda 
dc.contributor.authorWhittemore, Kurt 
dc.contributor.authorMoisés-Silva, Ana Carolina
dc.contributor.authorBosch, Fàtima
dc.contributor.authorBlasco , MA 
dc.date.accessioned2018-11-15T11:16:38Z
dc.date.available2018-11-15T11:16:38Z
dc.date.issued2018-08
dc.identifier.citationPLoS Genet. 2018; 14 (8): e1007562.es_ES
dc.identifier.issn1553-7404es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6599
dc.description.abstractShort and dysfunctional telomeres are sufficient to induce a persistent DNA damage response at chromosome ends, which leads to the induction of senescence and/or apoptosis and to various age-related conditions, including a group of diseases known as "telomere syndromes", which are provoked by extremely short telomeres owing to germline mutations in telomere genes. This opens the possibility of using telomerase activation as a potential therapeutic strategy to rescue short telomeres both in telomere syndromes and in age-related diseases, in this manner maintaining tissue homeostasis and ameliorating these diseases. In the past, we generated adeno-associated viral vectors carrying the telomerase gene (AAV9-Tert) and shown their therapeutic efficacy in mouse models of cardiac infarct, aplastic anemia, and pulmonary fibrosis. Although we did not observe increased cancer incidence as a consequence of Tert overexpression in any of those models, here we set to test the safety of AAV9-mediated Tert overexpression in the context of a cancer prone mouse model, owing to expression of oncogenic K-ras. As control, we also treated mice with AAV9 vectors carrying a catalytically inactive form of Tert, known to inhibit endogenous telomerase activity. We found that overexpression of Tert does not accelerate the onset or progression of lung carcinomas, even when in the setting of a p53-null background. These findings indicate that telomerase activation by using AAV9-mediated Tert gene therapy has no detectable cancer-prone effects in the context of oncogene-induced mouse tumors.es_ES
dc.description.sponsorshipAcknowledgmen ts We are indebted to D.Megias for microscopy analysis, to F. Mulero for molecular imaging, to Patricia Gonzalez for IHQand to R.Serrano for animal carees_ES
dc.language.isoenges_ES
dc.publisherPublic Library of Sciencees_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectTERT PROMOTER MUTATIONSes_ES
dc.subjectMOUSE TELOMERASEes_ES
dc.subjectCHROMOSOMAL INSTABILITYes_ES
dc.subjectCELLULAR SENESCENCEes_ES
dc.subjectBLADDER-CANCERes_ES
dc.subjectDNA-DAMAGEes_ES
dc.subjectMICEes_ES
dc.subjectADULTes_ES
dc.subjectEXPRESSIONes_ES
dc.titleAAV9-mediated telomerase activation does not accelerate tumorigenesis in the context of oncogenic K-Ras-induced lung canceres_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID30114189es_ES
dc.format.volume14es_ES
dc.format.number8es_ES
dc.format.pagee1007562es_ES
dc.identifier.doi10.1371/journal.pgen.1007562es_ES
dc.contributor.funderFundación Marcelo Botínes_ES
dc.contributor.funderMinisterio de Ciencia y Tecnología (España)es_ES
dc.description.peerreviewed
dc.identifier.e-issn1553-7404es_ES
dc.relation.publisherversionhttps://doi.org/10.1371/journal.pgen.1007562.es_ES
dc.identifier.journalPLoS geneticses_ES
dc.repisalud.institucionCNIOes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2013-45111-Res_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Atribución 4.0 Internacional
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