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dc.contributor.authorRodríguez Ruiz, Teresa
dc.contributor.authorMéndez Vales, Rosa
dc.contributor.authorCampo, Ana del
dc.contributor.authorJiménez Gámiz, Pilar
dc.contributor.authorAptsiauri, Natalia
dc.contributor.authorGarrido Torres-Puchol, Federico 
dc.contributor.authorRuiz-Cabello, Francisco
dc.date.accessioned2013-11-20T09:26:38Z
dc.date.available2013-11-20T09:26:38Z
dc.date.issued2007
dc.identifier.citationRodríguez, T.; et al. Distinct mechanisms of loss of IFN-gamma mediated HLA class I inducibility in two melanoma cell lines. BMC Cancer, 7: 34 (2007). [http://hdl.handle.net/10481/29167]es_ES
dc.identifier.issn1471-2407
dc.identifier.otherdoi: 10.1186/1471-2407-7-34
dc.identifier.otherPMCID: PMC1808467
dc.identifier.urihttp://hdl.handle.net/10481/29167
dc.description.abstractBackground The inability of cancer cells to present antigen on the cell surface via MHC class I molecules is one of the mechanisms by which tumor cells evade anti-tumor immunity. Alterations of Jak-STAT components of interferon (IFN)-mediated signaling can contribute to the mechanism of cell resistance to IFN, leading to lack of MHC class I inducibility. Hence, the identification of IFN-γ-resistant tumors may have prognostic and/or therapeutic relevance. In the present study, we investigated a mechanism of MHC class I inducibility in response to IFN-γ treatment in human melanoma cell lines.es_ES
dc.description.abstractMethods Basal and IFN-induced expression of HLA class I antigens was analyzed by means of indirect immunofluorescence flow cytometry, Western Blot, RT-PCR, and quantitative real-time RT-PCR (TaqMan® Gene Expression Assays). In demethylation studies cells were cultured with 5-aza-2'-deoxycytidine. Electrophoretic Mobility Shift Assay (EMSA) was used to assay whether IRF-1 promoter binding activity is induced in IFN-γ-treated cells.es_ES
dc.description.abstractResults Altered IFN-γ mediated HLA-class I induction was observed in two melanoma cells lines (ESTDAB-004 and ESTDAB-159) out of 57 studied, while treatment of these two cell lines with IFN-α led to normal induction of HLA class I antigen expression. Examination of STAT-1 in ESTDAB-004 after IFN-γ treatment demonstrated that the STAT-1 protein was expressed but not phosphorylated. Interestingly, IFN-α treatment induced normal STAT-1 phosphorylation and HLA class I expression. In contrast, the absence of response to IFN-γ in ESTDAB-159 was found to be associated with alterations in downstream components of the IFN-γ signaling pathway.es_ES
dc.description.abstractConclusion We observed two distinct mechanisms of loss of IFN-γ inducibility of HLA class I antigens in two melanoma cell lines. Our findings suggest that loss of HLA class I induction in ESTDAB-004 cells results from a defect in the earliest steps of the IFN-γ signaling pathway due to absence of STAT-1 tyrosine-phosphorylation, while absence of IFN-γ-mediated HLA class I expression in ESTDAB-159 cells is due to epigenetic blocking of IFN-regulatory factor 1 (IRF-1) transactivation.es_ES
dc.description.sponsorshipThis work was supported by grants from the Fondo de Investigaciones Sanitarias (FIS), Red Genomica del Cancer (C03/10), Plan Andaluz de Investigacion, Servicio Andaluz de Salud (SAS) in Spain, from the ESTDAB project (contract no. QLRI-CT-2001-01325), from the European Network for the identification and validation of Antigens and biomarkers in Cancer and their application in clinical Tumor immunology (ENACT, contract No. 503306), and from the European Cancer Immunotherapy project (OJ2004/C158, 518234).es_ES
dc.language.isoenges_ES
dc.publisherBiomed Centrales_ES
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs 3.0 Licensees_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es_ES
dc.subjectAntineoplastic agents es_ES
dc.subjectEpigenesises_ES
dc.subjectGenes es_ES
dc.subjectHLA antigentses_ES
dc.subjectMelanoma es_ES
dc.subjectSkin neoplasmses_ES
dc.subjectIRF1 proteines_ES
dc.subjectInterferon regulatory factor-1es_ES
dc.titleDistinct mechanisms of loss of IFN-gamma mediated HLA class I inducibility in two melanoma cell lineses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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