Özet:

OBJECTIVE This study aimed to determine the epigenetic basis of drug resistance mechanisms developed in MCF-7 breast cancer cell line that is resistant to an anticancer agent paclitaxel. Thus, we investigated the effects of the changes in DNA level on gene expression profile and proposed methods of inhibiting resistance by DNA modifications. METHODS We investigated the epigenetic basis of acquired drug resistance in whole genome by comparing chromosome immunoprecipitation in paclitaxel-resistant MCF-7 (MCF-7/Pac) cells and in drug-sensitive (MCF-7/S) cells. For this analysis, DNA samples from both cell lines were immunoprecipitated and labeled with Cy3 and Cy5 fluorescent dyes. Hybridization and array scanning was performed with Agilent all-Genome Microarray platform that was designed to detect DNA methylation. The obtained highthroughput information was analyzed with a bioinformatics analysis program. RESULTS The results showed that demethylation and epigenetic modulation of the DNA regions encoding 90 genes are significant in the development of multiple drug resistance (MDR) in breast cancer. Some of these genes, ICAM4, COX6B2, ITGB8, SLC39A4, TUBB2C, COL6A1, DAPK1, RUNX3, SLC35F3, and MAP6, are important players in the development of drug resistance and cancer stem cells. CONCLUSION Studies on reversing multidrug resistance can be carried out by DNA modification or methylation of target genes regions on DNA. The results presented in this study may shed light on drug development studies to make DNA modifications.

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