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dc.contributor.authorWickström, Malin
dc.contributor.authorDyberg, Cecilia
dc.contributor.authorMilosevic, Jelena
dc.contributor.authorEinvik, Christer
dc.contributor.authorCalero, Raul
dc.contributor.authorSveinbjørnsson, Baldur
dc.contributor.authorSandén, Emma
dc.contributor.authorDarabi, Anna
dc.contributor.authorSiesjö, Peter
dc.contributor.authorKool, Marcel
dc.contributor.authorKogner, Per
dc.contributor.authorBaryawno, Ninib
dc.contributor.authorJohnsen, John Inge
dc.date.accessioned2016-02-18T13:12:53Z
dc.date.available2016-02-18T13:12:53Z
dc.date.issued2015-11-25
dc.description.abstractThe DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) is commonly overexpressed in cancers and is implicated in the development of chemoresistance. The use of drugs inhibiting MGMT has been hindered by their haematologic toxicity and inefficiency. As a different strategy to inhibit MGMT we investigated cellular regulators of MGMT expression in multiple cancers. Here we show a significant correlation between Wnt signalling and MGMT expression in cancers with different origin and confirm the findings by bioinformatic analysis and immunofluorescence. We demonstrate Wnt-dependent MGMT gene expression and cellular co-localization between active β-catenin and MGMT. Pharmacological or genetic inhibition of Wnt activity downregulates MGMT expression and restores chemosensitivity of DNA-alkylating drugs in mouse models. These findings have potential therapeutic implications for chemoresistant cancers, especially of brain tumours where the use of temozolomide is frequently used in treatment.en_US
dc.descriptionPublished version also available at <a href=http://dx.doi.org/10.1038/ncomms9904>http://dx.doi.org/10.1038/ncomms9904</a>en_US
dc.identifier.citationNature Communications 2015, 6:8904en_US
dc.identifier.issn2041-1723
dc.identifier.otherFRIDAID 1295120
dc.identifier.other10.1038/ncomms9904
dc.identifier.urihttp://hdl.handle.net/10037/8510
dc.identifier.urnURN:NBN:no-uit_munin_8080
dc.language.isoengen_US
dc.publisherNature Publishing Groupen_US
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en_US
dc.titleWnt/β-catenin pathway regulates MGMT gene expression in cancer and inhibition of Wnt signalling prevents chemoresistanceen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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