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Cisplatin resistance conferred by the RAD51D (E233G) genetic variant is dependent upon p53 status in human breast carcinoma cell lines
Author(s) -
Nadkarni Aditi,
Rajesh Preeti,
Ruch Randall J.,
Pittman Douglas L.
Publication year - 2009
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20545
Subject(s) - biology , rad51 , homologous recombination , cisplatin , dna repair , cancer research , allele , genetics , phenotype , gene , chemotherapy
RAD51D , a paralog of the mammalian RAD51 gene, contributes towards maintaining genomic integrity by homologous recombination DNA repair and telomere maintenance. A RAD51D variant, E233G, was initially identified as a potential susceptibility allele in high‐risk, site‐specific, familial breast cancer. We describe in this report that the Rad51d (E233G) genetic variant confers increased cisplatin resistance and cell growth phenotypes in human breast carcinoma cell lines with a mutant p53 gene (BT20 and T47D) but not with a wild‐type p53 gene (MCF‐7). Treatment with a p53 specific inhibitor, pifithrin α, restored this resistant phenotype in the MCF‐7 cell line. Additionally, Rad51d (E233G) conferred increased cisplatin resistance of an MCF7 cell line in which p53 expression was stably knocked down by shRNAp53, indicating that the effect of this variant is dependent upon p53 status. Further study of Rad51d (E233G) will provide mechanistic insight towards the role of RAD51D in cellular response to anticancer agents and as a potential target for cancer therapy. © 2009 Wiley‐Liss, Inc.