C-myc amplification altered the gene expression of ABC- and SLC-transporters in human breast epithelial cells

Abstract

The present study aimed to investigate the effect of c-Myc overexpression on the gene expression and functional activity of major drug transporters in breast epithelial cells. In order to reflect c-Myc overexpressed epithelial cells, MCF10A cells (human mammary epithelial cells) stably expressing c-Myc (c-Myc-MCF10A cells) have been established by retroviral infection and then the effect of c-Myc activation on the gene expression and functional activity of 16 influx and efflux transporters was examined in c-Myc-MCF10A cells. In RT-PCR analysis, the quantitative difference in transporters' gene expression profiles was observed after c-Myc activation. Western blot analysis also indicated that the protein expression of some transporters (MCT1, OCT1, MRP1, MRP2 and BCRP) increased by c-Myc overexpression. In parallel to the alteration in gene expression, functional activity studies indicated that the cellular uptake of benzoic acid, MPP+, calcein-AM, H33342, representative substrates of MCT1, OCT1, MRPs and BCRP, respectively, was significantly (p < 0.05) altered by c-Myc overexpression. In conclusion, c-Myc amplification appeared to be coupled with the modulation of gene expression of certain drug transporters in human breast epithelial cells.