Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/6672
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dc.contributor.authorBouralexis, S.-
dc.contributor.authorFindlay, D.-
dc.contributor.authorAtkins, G.-
dc.contributor.authorLabrinidis, A.-
dc.contributor.authorHay, S.-
dc.contributor.authorEvdokiou, A.-
dc.date.issued2003-
dc.identifier.citationBritish Journal of Cancer, 2003; 89(1):206-214-
dc.identifier.issn0007-0920-
dc.identifier.issn1532-1827-
dc.identifier.urihttp://hdl.handle.net/2440/6672-
dc.description© 2003 Cancer Research UK-
dc.description.abstractApo2 ligand (Apo2L, also known as TRAIL) is a member of the tumour necrosis factor (TNF) family of cytokines that selectively induces the death of cancer cells, but not of normal cells. We observed that recombinant Apo2L/TRAIL was proapoptotic in early-passage BTK-143 osteogenic sarcoma cells, inducing 80% cell death during a 24 h treatment period. Apo2L/TRAIL-induced apoptosis was blocked by caspase inhibition. With increasing passage in culture, BTK-143 cells became progressively resistant to the apoptotic effects of Apo2L/TRAIL . RNA and flow cytometric analysis demonstrated that resistance to Apo2L/TRAIL was paralleled by progressive acquisition of the decoy receptor, DcR2. Blocking of DcR2 function with a specific anti-DcR2 antibody restored sensitivity to Apo2L/TRAIL in a dose-dependent manner. Importantly, treatment of resistant cells with the chemotherapeutic agents doxorubicin, cisplatin and etoposide reversed the resistance to Apo2L/TRAIL, which was associated with drug-induced upregulation of mRNA encoding the death receptors DR4 and DR5. BTK-143 cells thus represent a useful model system to investigate both the mechanisms of acquisition of resistance of tumour cells to Apo2L/TRAIL and the use of conventional drugs and novel agents to overcome resistance to Apo2L/TRAIL.-
dc.description.statementofresponsibilityS Bouralexis, D M Findlay, G J Atkins, A Labrinidis, S Hay & A Evdokiou-
dc.language.isoen-
dc.publisherChurchill Livingstone-
dc.source.urihttp://dx.doi.org/10.1038/sj.bjc.6601021-
dc.subjectDcR2-
dc.subjectApo2L/TRAIL-
dc.subjectosteosarcoma-
dc.subjectresistance-
dc.subjectchemotherapy-
dc.subjectapoptosis-
dc.titleProgressive resistance of BTK-143 osteosarcoma cells to Apo2L/TRAIL-induced apoptosis is mediated by acquisition of DcR2/TRAIL-R4 expression: resensitisation with chemotherapy-
dc.typeJournal article-
dc.identifier.doi10.1038/sj.bjc.6601021-
pubs.publication-statusPublished-
dc.identifier.orcidAtkins, G. [0000-0002-3123-9861]-
dc.identifier.orcidEvdokiou, A. [0000-0001-8321-9806]-
Appears in Collections:Aurora harvest 5
Orthopaedics and Trauma publications

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