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<OAI-PMH schemaLocation=http://www.openarchives.org/OAI/2.0/ http://www.openarchives.org/OAI/2.0/OAI-PMH.xsd> <responseDate>2018-01-15T18:35:39Z</responseDate> <request identifier=oai:HAL:inserm-00814096v1 verb=GetRecord metadataPrefix=oai_dc>http://api.archives-ouvertes.fr/oai/hal/</request> <GetRecord> <record> <header> <identifier>oai:HAL:inserm-00814096v1</identifier> <datestamp>2017-12-21</datestamp> <setSpec>type:ART</setSpec> <setSpec>subject:sdv</setSpec> <setSpec>collection:INSERM</setSpec> <setSpec>collection:UNIV-AG</setSpec> <setSpec>collection:IFR140</setSpec> <setSpec>collection:IRSET</setSpec> <setSpec>collection:UNIV-RENNES1</setSpec> <setSpec>collection:IRSET-SMLF</setSpec> <setSpec>collection:BIOSIT</setSpec> <setSpec>collection:UR1-UFR-SVE</setSpec> <setSpec>collection:STATS-UR1</setSpec> <setSpec>collection:UR1-HAL</setSpec> <setSpec>collection:EHESP</setSpec> <setSpec>collection:USPC</setSpec> <setSpec>collection:UR1-SDV</setSpec> <setSpec>collection:IRSET-5</setSpec> <setSpec>collection:UNIV-ANGERS</setSpec> </header> <metadata><dc> <publisher>HAL CCSD</publisher> <title lang=en>MAPK signaling in cisplatin-induced death: predominant role of ERK1 over ERK2 in human hepatocellular carcinoma cells.</title> <creator>Guégan, Jean-Philippe</creator> <creator>Ezan, Frédéric</creator> <creator>Théret, Nathalie</creator> <creator>Langouët, Sophie</creator> <creator>Baffet, Georges</creator> <contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor> <contributor>Institut National de la Santé et de la Recherche Médicale (Inserm); Université de Rennes 1; Rennes Métropole and Ligue contre le cancer du Grand Ouest. Ministère de l'Enseignement Supérieur et de la Recherche; the Fondation ARC (20120604652) (to JP.G.)</contributor> <description>International audience</description> <source>ISSN: 0143-3334</source> <source>EISSN: 1460-2180</source> <source>Carcinogenesis</source> <publisher>Oxford University Press (OUP)</publisher> <identifier>inserm-00814096</identifier> <identifier>http://www.hal.inserm.fr/inserm-00814096</identifier> <source>http://www.hal.inserm.fr/inserm-00814096</source> <source>Carcinogenesis, Oxford University Press (OUP), 2013, 34 (1), pp.38-47. 〈10.1093/carcin/bgs317〉</source> <identifier>DOI : 10.1093/carcin/bgs317</identifier> <relation>info:eu-repo/semantics/altIdentifier/doi/10.1093/carcin/bgs317</relation> <identifier>PUBMED : 23042098</identifier> <relation>info:eu-repo/semantics/altIdentifier/pmid/23042098</relation> <language>en</language> <subject>[SDV.CAN] Life Sciences [q-bio]/Cancer</subject> <subject>[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology</subject> <type>info:eu-repo/semantics/article</type> <type>Journal articles</type> <description lang=en>Hepatocellular carcinoma treatment by arterial infusion of cis-diamminedichloroplatinum-II (cisplatin) exhibits certain therapeutic efficacy. However, optimizations are required and the mechanisms underlying cisplatin proapoptotic effect remain unclear. The mitogen-activated protein kinase (MAPK) pathway plays a key role in cell response to cisplatin and the functional specificity of the isoform MAPK/ERK kinase 1 and 2 (MEK1/2) and ERK1/2 could influence this response. The individual contribution of each kinase on cisplatin-induced death was thus analyzed after a transient or stable specific inhibition by RNA interference in the human hepatocellular carcinoma cells Huh-7 or in knockout mice. We demonstrated here that ERK1 played a predominant role over ERK2 in cisplatin-induced death, whereas MEK1 and MEK2 acted in a redundant manner. Indeed, at clinically relevant concentrations of cisplatin, ERK1 silencing alone was sufficient to protect cells from cisplatin-induced death both in vitro, in Huh-7 cells and ERK1(-/-) hepatocytes, and in vivo, in ERK1-deficient mice. Moreover, we showed that ERK1 activity correlated with the induction level of the proapoptotic BH3-only protein Noxa, a critical mediator of cisplatin toxicity. On the contrary, ERK2 inhibition upregulated ERK1 activity, favored Noxa induction and sensitized hepatocarcinoma cells to cisplatin. Our results point to a crucial role of ERK1 in cisplatin-induced proapoptotic signal and lead us to propose that ERK2-specific targeting could improve the efficacy of cisplatin therapy by increasing ERK1 prodeath functions.</description> <date>2013-01</date> </dc> </metadata> </record> </GetRecord> </OAI-PMH>