Comparative gene expression profiling of human metallothionein-3 up-regulation in neuroblastoma cells and its impact on susceptibility to cisplatin

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dc.contributor.authorMerlos Rodrigo, Miguel Ángelcs
dc.contributor.authorDostálová, Simonacs
dc.contributor.authorBuchtelová, Hanacs
dc.contributor.authorStrmiska, Vladislavcs
dc.contributor.authorMichálek, Petrcs
dc.contributor.authorKřížková, Soňacs
dc.contributor.authorVícha, Alešcs
dc.contributor.authorEckschlager, Tomášcs
dc.contributor.authorStiborová, Mariecs
dc.contributor.authorHeger, Zbyněkcs
dc.contributor.authorAdam, Vojtěchcs
dc.coverage.issue4cs
dc.coverage.volume9cs
dc.date.accessioned2020-08-04T11:04:13Z
dc.date.available2020-08-04T11:04:13Z
dc.date.issued2018-01-12cs
dc.description.abstractHuman metallothionein-3 (hMT-3), also known as growth inhibitory factor, is predominantly expressed in the central nervous system. hMT-3 is presumed to participate in the processes of heavy metal detoxification, regulation of metabolism and protection against oxidative damage of free radicals in the central nervous system; thus, it could play important neuromodulatory and neuroprotective roles. However, the primary functions of hMT-3 and the mechanism underlying its multiple functions in neuroblastoma have not been elucidated so far. First, we confirmed relatively high expression of hMT-3 encoding mRNA in biopsies (n = 23) from high-risk neuroblastoma subjects. Therefore, we focused on investigation of the impact of hMT-3 up-regulation in N-Myc amplifying neuroblastoma cells. The differentially up-regulated genes involved in biological pathways related to cellular senescence and cell cycle were identified using electrochemical microarray with consequent bioinformatic processing. Further, as experimental verification of microarray data, the cytotoxicity of the cisplatin (CDDP) was examined in hMT-3 and mock cells by MTT and clonogenic assays. Overall, our data strongly suggest that up-regulation of hMT-3 positively correlates with the genes involved in oncogene-induced senescence (CDKN2B and ANAPC5) or apoptosis (CASP4). Moreover, we identified a significant increase in chemoresistance to cisplatin (CDDP) due to hMT-3 up-regulation (24IC(50): 7.5 vs. 19.8 mu g/ml), indicating its multipurpose biological significance.en
dc.formattextcs
dc.format.extent4427-4439cs
dc.format.mimetypeapplication/pdfcs
dc.identifier.citationOncotarget. 2018, vol. 9, issue 4, p. 4427-4439.en
dc.identifier.doi10.18632/oncotarget.23333cs
dc.identifier.issn1949-2553cs
dc.identifier.other145110cs
dc.identifier.urihttp://hdl.handle.net/11012/72413
dc.language.isoencs
dc.publisherImpact Journalscs
dc.relation.ispartofOncotargetcs
dc.relation.urihttp://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=23333&path[]=73538cs
dc.rightsCreative Commons Attribution 3.0 Unportedcs
dc.rights.accessopenAccesscs
dc.rights.sherpahttp://www.sherpa.ac.uk/romeo/issn/1949-2553/cs
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/cs
dc.subjectapoptosisen
dc.subjectcisplatinen
dc.subjectchemoresistanceen
dc.subjectmetallothioneinen
dc.subjectoncogene-induced senescenceen
dc.titleComparative gene expression profiling of human metallothionein-3 up-regulation in neuroblastoma cells and its impact on susceptibility to cisplatinen
dc.type.driverarticleen
dc.type.statusPeer-revieweden
dc.type.versionpublishedVersionen
sync.item.dbidVAV-145110en
sync.item.dbtypeVAVen
sync.item.insts2020.08.04 13:04:13en
sync.item.modts2020.08.04 12:41:52en
thesis.grantorVysoké učení technické v Brně. Středoevropský technologický institut VUT. Chytré nanonástrojecs
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