Gene expression alterations in doxorubicin resistant MCF7 breast cancer cell line

Many molecular mechanisms contribute to the development of doxorubicin resistance and different cancers can express wide and diverse arrays of drug-resistance genes. The aim of this study was to identify the changes in gene expression associated with the development of doxorubicin resistance in MCF7 breast cancer cell line. The doxorubicin resistant MCF7 cell line was developed by stepwise selection of MCF7 cells and was tested using the MTT assay. The alterations in gene expression were examined using the real-time based PCR array. The findings showed an up-regulation of many phase I/II metabolizing genes, specifically, the CYP1A1 and the CYP1A2 that were up-regulated by 206- and 96-fold respectively. Drug efflux pump genes were also up-regulated profoundly. TOP2A was strongly down-regulated by 202-fold. Many other changes were observed in genes crucial for cell cycle, apoptosis and DNA repair. The findings of this project imply that the development of doxorubicin resistance is a multi-factorial process.

► The process of MCF7 resistant toward doxorubicin is multi-factorial.
► CYP1A1 and CYP1A2 were up-regulated by 206- and 96-fold respectively.
► Topo2A is the only topoisomerase subtype to be down-regulated by 202 fold.
► Varapamil has partial ability to re-sensitize resistant cell to doxorubicin.
► Many transporter genes have been up-regulated.