A multidrug resistance transporter from human MCF-7 breast cancer cells

TLDR

MCF‑7/AdrVp is a multidrug‑resistant breast cancer subline that reduces intracellular anthracycline accumulation through an ATP‑dependent mechanism without overexpressing known transporters such as P‑glycoprotein. RNA fingerprinting revealed an overexpressed 2.4‑kb mRNA encoding a 663‑aa ATP‑binding cassette transporter, BCRP, whose enforced expression confers resistance to multiple anthracyclines and enhances ATP‑dependent efflux, demonstrating BCRP’s central role in the MDR phenotype.

Abstract

MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of overexpression of known multidrug resistance transporters such as P glycoprotein or the multidrug resistance protein. RNA fingerprinting led to the identification of a 2.4-kb mRNA that is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells. The mRNA encodes a 663-aa member of the ATP-binding cassette superfamily of transporters that we term breast cancer resistance protein (BCRP). Enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux of rhodamine 123 in the cloned transfected cells. BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells.