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dc.contributor.authorBARR, MARTINen
dc.contributor.authorO'LEARY, JOHNen
dc.contributor.authorGRAY, STEVENen
dc.date.accessioned2015-02-16T16:23:21Z
dc.date.available2015-02-16T16:23:21Z
dc.date.issued2013en
dc.date.submitted2013en
dc.identifier.citationBarr MP, Gray SG, Hoffmann AC, Hilger RA, Thomale J, O Flaherty JD, Fennell DA, Richard D, O Leary JJ, O'Byrne KJ., Generation and characterisation of Cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature., PloS one, 8, 1, 2013, e54193en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/73240
dc.descriptionPUBLISHEDen
dc.description.abstractIntroduction: Inherent and acquired cisplatin resistance reduces the effectiveness of this agent in the management of non- small cell lung cancer (NSCLC). Understanding the molecular mechanisms underlying this process may result in the development of novel agents to enhance the sensitivity of cisplatin. Methods: An isogenic model of cisplatin resistance was generated in a panel of NSCLC cell lines (A549, SKMES-1, MOR, H460). Over a period of twelve months, cisplatin resistant (CisR) cell lines were derived from original, age-matched parent cells (PT) and subsequently characterized. Proliferation (MTT) and clonogenic survival assays (crystal violet) were carried out between PT and CisR cells. Cellular response to cisplatin-induced apoptosis and cell cycle distribution were examined by FACS analysis. A panel of cancer stem cell and pluripotent markers was examined in addition to the EMT proteins, c-Met and b -catenin. Cisplatin-DNA adduct formation, DNA damage ( c H2AX) and cellular platinum uptake (ICP-MS) was also assessed. Results: Characterisation studies demonstrated a decreased proliferative capacity of lung tumour cells in response to cisplatin, increased resistance to cisplatin-induced cell death, accumulation of resistant cells in the G0/G1 phase of the cell cycle and enhanced clonogenic survival ability. Moreover, resistant cells displayed a putative stem-like signature with increased expression of CD133 + /CD44 + cells and increased ALDH activity relative to their corresponding parental cells. The stem cell markers, Nanog, Oct-4 and SOX-2, were significantly upregulated as were the EMT markers, c-Met and b -catenin. While resistant sublines demonstrated decreased uptake of cisplatin in response to treatment, reduced cisplatin-GpG DNA adduct formation and significantly decreased c H2AX foci were observed compared to parental cell lines. Conclusion: Our results identified cisplatin resistant subpopulations of NSCLC cells with a putative stem-like signature, providing a further understanding of the cellular events associated with the cisplatin resistance phenotype in lung cancer.en
dc.format.extente54193en
dc.language.isoenen
dc.language.isoenen
dc.relation.ispartofseriesPloS oneen
dc.relation.ispartofseries8en
dc.relation.ispartofseries1en
dc.rightsYen
dc.subjectcisplatin resistanceen
dc.subject.lcshcisplatin resistanceen
dc.titleGeneration and characterisation of Cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature.en
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/olearyjjen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/barrmaen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/graysten
dc.identifier.rssinternalid83473en
dc.identifier.doihttp://dx.doi.org/ 10.1371/journal.pone.0054193en
dc.rights.ecaccessrightsopenAccess
dc.subject.TCDThemeCanceren
dc.subject.TCDTagBiomedical sciencesen
dc.identifier.rssuri23349823en


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