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ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair

Stordal, Britta and Davey, Ross (2009) ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair. Cancer Chemotherapy and Pharmacology, 63 (4). pp. 661-672. ISSN 1432-0843

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Abstract

Background: The H69CIS200 and H69OX400 cell lines are novel models of low-level platinum-drug resistance. Resistance was not associated with increased cellular glutathione or decreased accumulation of platinum, rather the resistant cell lines have a cell cycle alteration allowing them to rapidly proliferate post drug treatment. Results: A decrease in ERCC1 protein expression and an increase in RAD51B foci activity was observed in association with the platinum induced cell cycle arrest but these changes did not correlate with resistance or altered DNA repair capacity. The H69 cells and resistant cell lines have a p53 mutation and consequently decrease expression of p21 in response to platinum drug treatment, promoting progression of the cell cycle instead of increasing p21 to maintain the arrest. Conclusion: Decreased ERCC1 protein and increased RAD51B foci may in part be mediating the maintenance of the cell cycle arrest in the sensitive cells. Resistance in the H69CIS200 and H69OX400 cells may therefore involve the regulation of ERCC1 and RAD51B independent of their roles in DNA repair. The novel mechanism of platinum resistance in the H69CIS200 and H69OX400 cells demonstrates the multifactorial nature of platinum resistance which can occur independently of alterations in DNA repair capacity and changes in ERCC1.

Item Type:Article (Published)
Refereed:Yes
Additional Information:The original publication is available at www.springerlink.com
Uncontrolled Keywords:Cisplatin; Oxaliplatin; Resistance; Cell Cycle; DNA Repair; ERCC1; RAD51B; p21; Small Cell Lung Cancer;
Subjects:Biological Sciences > Cell biology
Medical Sciences > Cancer
DCU Faculties and Centres:Research Initiatives and Centres > National Institute for Cellular Biotechnology (NICB)
Publisher:Springer Berlin / Heidelberg
Official URL:http://dx.doi.org/10.1007/s00280-008-0783-x
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 License. View License
Funders:Bill Walsh Cancer Research Trust
ID Code:2203
Deposited On:08 Dec 2008 13:09 by Britta Stordal. Last Modified 22 Mar 2009 09:27

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