dc.contributor.author | BARR, MARTIN | en |
dc.contributor.author | O'LEARY, JOHN | en |
dc.contributor.author | GRAY, STEVEN | en |
dc.date.accessioned | 2015-02-16T16:23:21Z | |
dc.date.available | 2015-02-16T16:23:21Z | |
dc.date.issued | 2013 | en |
dc.date.submitted | 2013 | en |
dc.identifier.citation | Barr 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, e54193 | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/73240 | |
dc.description | PUBLISHED | en |
dc.description.abstract | Introduction:
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.extent | e54193 | en |
dc.language.iso | en | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | PloS one | en |
dc.relation.ispartofseries | 8 | en |
dc.relation.ispartofseries | 1 | en |
dc.rights | Y | en |
dc.subject | cisplatin resistance | en |
dc.subject.lcsh | cisplatin resistance | en |
dc.title | Generation and characterisation of Cisplatin-resistant non-small cell lung cancer cell lines displaying a stem-like signature. | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/olearyjj | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/barrma | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/grayst | en |
dc.identifier.rssinternalid | 83473 | en |
dc.identifier.doi | http://dx.doi.org/ 10.1371/journal.pone.0054193 | en |
dc.rights.ecaccessrights | openAccess | |
dc.subject.TCDTheme | Cancer | en |
dc.subject.TCDTag | Biomedical sciences | en |
dc.identifier.rssuri | 23349823 | en |