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dc.contributor.author
Grasso, Daniel Hector  
dc.contributor.author
Bintz, Jennifer  
dc.contributor.author
Lomberk, Gwen  
dc.contributor.author
Molejon, Maria Ines  
dc.contributor.author
Loncle, Celine  
dc.contributor.author
Garcia, Maria Noé  
dc.contributor.author
Lopez Millian, Maria Belen  
dc.contributor.author
Urrutia, Raul  
dc.contributor.author
Iovanna, Juan  
dc.date.available
2018-06-05T21:53:44Z  
dc.date.issued
2015-11  
dc.identifier.citation
Grasso, Daniel Hector; Bintz, Jennifer; Lomberk, Gwen; Molejon, Maria Ines; Loncle, Celine; et al.; Pivotal Role of the Chromatin Protein Nupr1 in Kras-Induced Senescence and Transformation; Nature Publishing Group; Scientific Reports; 5; 1754; 11-2015; 1-11  
dc.identifier.issn
2045-2322  
dc.identifier.uri
http://hdl.handle.net/11336/47430  
dc.description.abstract
Nupr1 is a chromatin protein, which cooperates with Kras(G12D) to induce PanIN formation and pancreatic cancer development in mice, though the molecular mechanisms underlying this effect remain to be fully characterized. In the current study, we report that Nupr1 acts as a gene modifier of the effect of Kras(G12D)-induced senescence by regulating Dnmt1 expression and consequently genome-wide levels of DNA methylation. Congruently, 5-aza-2'-deoxycytydine, a general inhibitor of DNA methylation, reverses the Kras(G12D)-induced PanIN development by promoting senescence. This requirement of Nupr1 expression, however, is not restricted to the pancreas since in lung of Nupr1(-/-) mice the expression of Kras(G12D) induces senescence instead of transformation. Therefore, mechanistically this data reveals that epigenetic events, at least at the level of DNA methylation, modulate the functional outcome of common genetic mutations, such as Kras(G12D), during carcinogenesis. The biomedical relevance of these findings lies in that they support the rational for developing similar therapeutic interventions in human aimed at controlling either the initiation or progression of cancer.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Nature Publishing Group  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
Pdac  
dc.subject
Oncogene-Induced Senescence  
dc.subject
Nupr1  
dc.subject
Dnmt1  
dc.subject.classification
Inmunología  
dc.subject.classification
Medicina Básica  
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD  
dc.title
Pivotal Role of the Chromatin Protein Nupr1 in Kras-Induced Senescence and Transformation  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2018-06-04T21:15:45Z  
dc.journal.volume
5  
dc.journal.number
1754  
dc.journal.pagination
1-11  
dc.journal.pais
Reino Unido  
dc.journal.ciudad
Londres  
dc.description.fil
Fil: Grasso, Daniel Hector. Centre de Recherche en Cancérologie de Marseille; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina  
dc.description.fil
Fil: Bintz, Jennifer. Centre de Recherche en Cancérologie de Marseille; Francia  
dc.description.fil
Fil: Lomberk, Gwen. Mayo Clinic; Estados Unidos  
dc.description.fil
Fil: Molejon, Maria Ines. Centre de Recherche en Cancérologie de Marseille; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina  
dc.description.fil
Fil: Loncle, Celine. Centre de Recherche en Cancérologie de Marseille; Francia  
dc.description.fil
Fil: Garcia, Maria Noé. Centre de Recherche en Cancérologie de Marseille; Francia  
dc.description.fil
Fil: Lopez Millian, Maria Belen. Centre de Recherche en Cancérologie de Marseille; Francia  
dc.description.fil
Fil: Urrutia, Raul. Mayo Clinic; Estados Unidos  
dc.description.fil
Fil: Iovanna, Juan. Centre de Recherche en Cancérologie de Marseille; Francia  
dc.journal.title
Scientific Reports  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/srep17549  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/srep17549