Sequencing of parental and chemotherapy-resistant breast cancer cell lines
This study aimed to determine whether chemotherapy resistance is associated with DNA methylation changes and to evaluate the potency of DNA methyltransferase inhibitor decitabine (DAC) to reverse these alterations, thereby sensitizing resistant cells to chemotherapy. We established paclitaxel (PAC)- and doxorubicin (DOX)-resistant BC cell lines from luminal A (T47-D), triple-negative (MDA-MB-231), and HER2-positive trastuzumab-resistant (JIMT-1) subtypes. Resistant cells were characterized phenotypically and molecularly, including in vivo tumorigenicity assessment. Whole-genome DNA methylation profiling (EPIC v1.0 array), and transcriptomic analyses were performed on tumor xenografts derived from MDA-MB-231 parental and paclitaxel-resistant cells. An integrative analysis was performed to assess the impact of DAC treatment on DNA methylation and gene expression.