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

Article


Stordal, B. and Davey, R. 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. https://doi.org/10.1007/s00280-008-0783-x
TypeArticle
TitleERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair
AuthorsStordal, B. and Davey, R.
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.

KeywordsCisplatin; Oxaliplatin; Resistance; Cell cycle; DNA repair; ERCC1; RAD51B; p21; Small cell lung cancer
Research GroupBiomarkers for Cancer group
PublisherSpringer
JournalCancer Chemotherapy and Pharmacology
ISSN0344-5704
Electronic1432-0843
Publication dates
Online25 Jun 2008
Print01 Mar 2009
Publication process dates
Deposited28 Apr 2015
Accepted02 Jun 2008
Output statusPublished
Accepted author manuscript
Copyright Statement

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use (https://www.springernature.com/gp/open-research/policies/accepted-ma...) , but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s00280-008-0783-x

Digital Object Identifier (DOI)https://doi.org/10.1007/s00280-008-0783-x
Web of Science identifierWOS:000264114300011
LanguageEnglish
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