English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/130482
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
Exportar a otros formatos:

DC FieldValueLanguage
dc.contributor.authorSchönhuber, Nina-
dc.contributor.authorVarela, Ignacio-
dc.contributor.authorSaur, Dieter-
dc.date.accessioned2016-03-29T07:49:04Z-
dc.date.available2016-03-29T07:49:04Z-
dc.date.issued2014-
dc.identifierdoi: 10.1038/nm.3646-
dc.identifierissn: 1078-8956-
dc.identifiere-issn: 1546-170X-
dc.identifier.citationNature Medicine 20(11): 1340-1347 (2014)-
dc.identifier.urihttp://hdl.handle.net/10261/130482-
dc.descriptionPMCID: PMC4270133.-- et al.-
dc.description.abstractGenetically engineered mouse models (GEMMs) have dramatically improved our understanding of tumor evolution and therapeutic resistance. However, sequential genetic manipulation of gene expression and targeting of the host is almost impossible using conventional Cre-loxP-based models. We have developed an inducible dual-recombinase system by combining flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies to improve GEMMs of pancreatic cancer. This enables investigation of multistep carcinogenesis, genetic manipulation of tumor subpopulations (such as cancer stem cells), selective targeting of the tumor microenvironment and genetic validation of therapeutic targets in autochthonous tumors on a genome-wide scale. As a proof of concept, we performed tumor cell-autonomous and nonautonomous targeting, recapitulated hallmarks of human multistep carcinogenesis, validated genetic therapy by 3-phosphoinositide-dependent protein kinase inactivation as well as cancer cell depletion and show that mast cells in the tumor microenvironment, which had been thought to be key oncogenic players, are dispensable for tumor formation.-
dc.description.sponsorshipThis work was supported by funding from Deutsche Forschungsgemeinschaft (DFG SA 1374/4-1 to D.S. and SFB824, TP C9 to G.S. and D.S.), the Helmholtz Alliance Preclinical Comprehensive Cancer Center (to H.R.R., R.R., R.M.S. and D.S.), the German Cancer Consortium (DKTK) (to R.R., R.M.S. and D.S.), the Wilhelm-Sander Foundation (2012.084.1 to G.S.), the Spanish Ministerio de Economía y Competitividad subprograma Ramón y Cajal (I.V.), the European Union (ERC Advanced Grant No.233074 to H.R.R.), and the National Cancer Institute USA (R01 CA138265 to D.G.K. and CA155620 to A.M.L.).-
dc.publisherNature Publishing Group-
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/233074-
dc.relation.isversionofPostprint-
dc.rightsopenAccess-
dc.titleA next-generation dual-recombinase system for time and host specific targeting of pancreatic cancer-
dc.typeartículo-
dc.identifier.doi10.1038/nm.3646-
dc.relation.publisherversionhttp://dx.doi.org/10.1038/nm.3646-
dc.date.updated2016-03-29T07:49:04Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.contributor.funderNational Cancer Institute (US)-
dc.contributor.funderNational Institutes of Health (US)-
dc.contributor.funderEuropean Research Council-
dc.contributor.funderEuropean Commission-
dc.contributor.funderMinisterio de Economía y Competitividad (España)-
dc.contributor.funderWilhelm Sander Foundation-
dc.contributor.funderHelmholtz Association-
dc.contributor.funderGerman Research Foundation-
dc.contributor.funderDeutsches Krebsforschungszentrum-
dc.relation.csic-
dc.identifier.funderhttp://dx.doi.org/10.13039/100000002es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000781es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100008672es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100001659es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100008658es_ES
Appears in Collections:(IBBTEC) Artículos
Files in This Item:
File Description SizeFormat 
pancreaticancer.pdf3,22 MBAdobe PDFThumbnail
View/Open
Show simple item record
 

Related articles:


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