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dc.contributor.authorSandoval-Usme, María Claudia-
dc.contributor.authorGuerra, Borja-
dc.contributor.authorFernández-Pérez, Leandro-
dc.date.accessioned2015-11-05T13:46:43Z-
dc.date.available2015-11-05T13:46:43Z-
dc.date.issued2014-
dc.identifierdoi: 10.1371/journal.pone.0087769-
dc.identifierissn: 1932-6203-
dc.identifier.citationPLoS ONE 9(1): e87769 (2014)-
dc.identifier.urihttp://hdl.handle.net/10261/124571-
dc.descriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.-
dc.description.abstractRecent studies have demonstrated that statins reduce cell viability and induce apoptosis in various types of cancer cells. The molecular mechanisms underlying these effects are poorly understood. The JAK/STAT pathway plays an important role in the regulation of proliferation and apoptosis in many tissues, and its deregulation is believed to be involved in tumorigenesis and cancer. The physiological activation of STAT proteins by GH is rapid but transient in nature and its inactivation is regulated mainly by the expression of SOCS proteins. UMR-106 osteosarcoma cells express a GH-responsive JAK2/STAT5 signaling pathway, providing an experimental model to study the influence of statins on this system. In this study we investigated the actions of simvastatin on cell proliferation, migration, and invasion on UMR-106 cells and examined whether alterations in GH-stimulated JAK/STAT/SOCS signaling may be observed. Results showed that treatment of osteosarcoma cells with simvastatin at 3 to 10 μM doses decreases cell proliferation, migration, and invasion in a time-and dose-dependent manner. At the molecular level, although the mechanisms used by simvastatin are not entirely clear, the effect of the statin on the reduction of JAK2 and STAT5 phosphorylation levels may partially explain the decrease in the GH-stimulated STAT5 transcriptional activity. This effect correlated with a time- and dose-dependent increase of SOCS-3 expression levels in cells treated with simvastatin, a regulatory role that has not been previously described. Furthermore, the finding that simvastatin is capable of inducing SOCS-3 and CIS genes expression shows the potential of the JAK/STAT pathway as a therapeutic target, reinforcing the efficacy of simvastatin as chemotherapeutic drug for the treatment of osteosarcoma.-
dc.description.sponsorshipThis work was supported by grants-in-aid to LF-P from the Spanish Ministry of Science and Innovation with the funding of European Regional Development Fund-European Social Fund (SAF2003-02117 and SAF2006-07824) and grants to M.S.-G. from the National University of Colombia Research Council (DIB Grants 10879, 12243, 14233 and 16056).-
dc.publisherPublic Library of Science-
dc.relation.isversionofPublisher's version-
dc.rightsopenAccess-
dc.titleSimvastatin impairs growth hormone-activated signal transducer and activator of transcription (STAT) signaling pathway in UMR-106 osteosarcoma cells-
dc.typeArtículo-
dc.identifier.doi10.1371/journal.pone.0087769-
dc.relation.publisherversionhttp://dx.doi.org/10.1371/journal.pone.0087769-
dc.date.updated2015-11-05T13:46:43Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.rights.licensehttp://creativecommons.org/licenses/by/4.0/-
dc.contributor.funderUniversidad Nacional de Colombia-
dc.contributor.funderEuropean Commission-
dc.contributor.funderMinisterio de Ciencia e Innovación (España)-
dc.relation.csic-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100002753es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004837es_ES
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