Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/33005
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dc.contributor.authorPeña Rico, Miguel A.-
dc.contributor.authorCalvo-Vidal, María Nieves-
dc.contributor.authorVilallonga Planells, Ruth-
dc.contributor.authorMartínez Soler, Fina-
dc.contributor.authorGiménez Bonafé, Pepita-
dc.contributor.authorNavarro i Sabaté, Àurea-
dc.contributor.authorTortosa i Moreno, Avelina-
dc.contributor.authorBartrons Bach, Ramon-
dc.contributor.authorManzano Cuesta, Anna-
dc.date.accessioned2012-12-05T10:25:19Z-
dc.date.available2012-12-05T10:25:19Z-
dc.date.issued2011-11-
dc.identifier.issn0167-8140-
dc.identifier.urihttp://hdl.handle.net/2445/33005-
dc.description.abstractBackground and purpose: The TP53 induced glycolysis and apoptosis regulator (TIGAR) functions to lower fructose-2,6-bisphosphate (Fru-2,6-P2) levels in cells, consequently decreasing glycolysis and leading to the scavenging of reactive oxygen species (ROS), which correlate with a higher resistance to cell death. The decrease in intracellular ROS levels in response to TIGAR may also play a role in the ability of p53 to protect from the accumulation of genomic lesions. Given these good prospects of TIGAR for metabolic regulation and p53-response modulation, we analyzed the effects of TIGAR knockdown in U87MG and T98G glioblastoma-derived cell lines. Methods/results: After TIGAR-knockdown in glioblastoma cell lines, different metabolic parameters were assayed, showing an increase in Fru-2,6-P2, lactate and ROS levels, with a concomitant decrease in reduced glutathione (GSH) levels. In addition, cell growth was inhibited without evidence of apoptotic or autophagic cell death. In contrast, a clear senescent phenotype was observed. We also found that TIGAR protein levels were increased shortly after irradiation. In addition, avoiding radiotherapy-triggered TIGAR induction by gene silencing resulted in the loss of capacity of glioblastoma cells to form colonies in culture and the delay of DNA repair mechanisms, based in c-H2AX foci, leading cells to undergo morphological changes compatible with a senescent phenotype. Thus, the results obtained raised the possibility to consider TIGAR as a therapeutic target to increase radiotherapy effects. Conclusion: TIGAR abrogation provides a novel adjunctive therapeutic strategy against glial tumors by increasing radiation-induced cell impairment, thus allowing the use of lower radiotherapeutic doses.-
dc.format.extent8 p.-
dc.format.mimetypeapplication/pdf-
dc.language.isoeng-
dc.publisherElsevier B.V.-
dc.relation.isformatofVersió postprint del document publicat a: http://dx.doi.org/10.1016/j.radonc.2011.07.002-
dc.relation.ispartofRadiotherapy and Oncology, 2011, vol. 101, num. 1, p. 132-139-
dc.relation.urihttp://dx.doi.org/10.1016/j.radonc.2011.07.002-
dc.rights(c) Elsevier B.V., 2011-
dc.subject.classificationGlioma-
dc.subject.classificationProteïnes supressores de tumors-
dc.subject.otherGliomas-
dc.subject.otherTumor suppressor protei-
dc.titleTP53 induced glycolysis and apoptosis regulator (TIGAR) knockdown results in radiosensitization of glioma cells-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/acceptedVersion-
dc.identifier.idgrec600411-
dc.date.updated2012-12-05T10:25:19Z-
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess-
Appears in Collections:Articles publicats en revistes (Infermeria Fonamental i Medicoquirúrgica)

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