APM2 is a novel mediator of cisplatin resistance in a variety of cancer cell types regardless of p53 or MMR status

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DOIResolve DOI: http://doi.org/10.1002/ijc.24465
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TypeArticle
Journal titleInternational Journal of Cancer
Volume125
Issue5
Pages11931204; # of pages: 12
Subjectcisplatin; resistance; APM2; C10orf116; microarray; siRNA
AbstractCisplatin is one of the most widely used chemotherapeutics in the world today. Unfortunately, chemoresistance often develops hindering the effectiveness of the drug. Mismatch-repair (MMR) and p53 have previously been shown to be important determinants of cisplatin resistance and can contribute to cisplatin resistance clinically. Here, we have used cDNA microarray to identify several genes as up or downregulated in a previously described, cisplatin resistant, clone of the HCT116 cell line (HCT116-K). On followup, one gene, APM2, was found to promote cisplatin resistance when overexpressed in sensitive HCT116 clones. Furthermore, silencing APM2 in a panel of cell lines encompassing all combinations of p53 status and MMR proficiency (HCT116-K, HCT116, SW620, MCF7, PC-3 and OV2008) resulted in sensitization regardless of these 2 factors. In addition, silencing APM2 stably using shRNA also resulted in the sensitization of cells to cisplatin. More importantly, cisplatin inhibited the growth of APM2 silenced tumor xenografts (HCT116-K or OV2008 cells) significantly better than it inhibited the growth of xenografts carrying nontargeting control shRNAs. These findings represent a novel strategy that could be exploited to overcome cisplatin resistance in patients regardless of p53 status or ability to perform MMR.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biological Sciences
Peer reviewedYes
NPARC number15329310
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Record identifier60da92a0-ac36-40a6-b983-8f1d49a9553f
Record created2010-05-21
Record modified2016-05-09
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