Vis enkel innførsel

dc.contributor.authorHiyoshi, H
dc.contributor.authorAbdelhady, S
dc.contributor.authorSegerström, L
dc.contributor.authorSveinbjørnsson, Baldur
dc.contributor.authorNuriya, M
dc.contributor.authorLundgren, T
dc.contributor.authorDesfrere, L
dc.contributor.authorMiyakawa, A
dc.contributor.authorYasui, M.
dc.contributor.authorKogner, P
dc.contributor.authorJohnsen, JI
dc.contributor.authorAndang, M
dc.contributor.authorUhlén, P
dc.date.accessioned2013-03-13T10:32:54Z
dc.date.available2013-03-13T10:32:54Z
dc.date.issued2012
dc.description.abstractCellular quiescence is a state of reversible proliferation arrest that is induced by anti-mitogenic signals. The endogenous cardiac glycoside ouabain is a specific ligand of the ubiquitous sodium pump, Na,K-ATPase, also known to regulate cell growth through unknown signalling pathways. To investigate the role of ouabain/Na,K-ATPase in uncontrolled neuroblastoma growth we used xenografts, flow cytometry, immunostaining, comet assay, real-time PCR, and electrophysiology after various treatment strategies. The ouabain/Na,K-ATPase complex induced quiescence in malignant neuroblastoma. Tumour growth was reduced by >50% when neuroblastoma cells were xenografted into immune-deficient mice that were fed with ouabain. Ouabain-induced S-G2 phase arrest, activated the DNA-damage response (DDR) pathway marker γH2AX, increased the cell cycle regulator p21Waf1/Cip1 and upregulated the quiescence-specific transcription factor hairy and enhancer of split1 (HES1), causing neuroblastoma cells to ultimately enter G0. Cells re-entered the cell cycle and resumed proliferation, without showing DNA damage, when ouabain was removed. Conclusion: These findings demonstrate a novel action of ouabain/Na,K-ATPase as a regulator of quiescence in neuroblastoma, suggesting that ouabain can be used in chemotherapies to suppress tumour growth and/or arrest cells to increase the therapeutic index in combination therapies.en
dc.identifier.citationBritish Journal of Cancer 106(2012) nr. 11 s. 1807-1815en
dc.identifier.cristinIDFRIDAID 948085
dc.identifier.doihttp://dx.doi.org/10.1038/bjc.2012.159
dc.identifier.issn0007-0920
dc.identifier.urihttps://hdl.handle.net/10037/4981
dc.identifier.urnURN:NBN:no-uit_munin_4720
dc.language.isoengen
dc.publisherNature Publishing Groupen
dc.rights.accessRightsopenAccess
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical molecular biology: 711en
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk molekylærbiologi: 711en
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical microbiology: 715en
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk mikrobiologi: 715en
dc.titleQuiescence and gamma H2AX in neuroblastoma are regulated by ouabain/Na,K-ATPaseen
dc.typeJournal articleen
dc.typeTidsskriftartikkelen
dc.typePeer revieweden


Tilhørende fil(er)

Thumbnail
Thumbnail

Denne innførselen finnes i følgende samling(er)

Vis enkel innførsel