Cisplatin DNA Repair Oxaliplatin ERCC1 RAD51B Small Cell Lung Cancer
Stordal, B. and Davey R, ERCC1 expression and RAD51B activity correlate with cell cycle response to platinum drug treatment not DNA repair., Cancer Chemotherapy and Pharmacology, 63, 4, 2009, 661 - 672
Cancer Chemotherapy and Pharmacology;63, 4
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.
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