Gene expression data in Control, Doxorubicin-resistant, and Epirubicin-resistant breast cancer cells

Development of chemotherapy resistance is a critical barrier in cancer treatment. Increased reliance on mitochondrial metabolism has been described as a distinctive characteristic of resistant cancers, however it is unknown whether enhanced oxidative metabolism is an intrinsic property or whether the metabolic signature of resistant cancers is dependent on the therapeutics. In this study, we used microarrays to detail the differences in global gene expression between anthracycline-resistant and -sensitive breast cancer cells. Taken together with metabolomics, bioenergetics, and functional experiments, we show that two anthracyclines (doxorubicin and epirubicin) elicit distinct metabolic adaptations in breast cancer and that interfering with global metabolic regulators can overcome resistance to different therapeutic agents by their ability to simultaneously interfere with numerous metabolic pathways. We obtained MCF-7 breast cancer cells selected in increasing doses of doxorubicin or epirubicin, previously described in PMID 18980695 and GSE12115. Cells were cultured using the same media and grown at similar densities. Control (sensitive) cells were maintained in 0.1% DMSO, DoxR (doxorubicin-resistant) cells in 98.1 nM doxorubicin, and EpiR (epirubicin-resistant) cells in 852 nM epirubicin at all times. Each condition has 3 biological replicates.