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

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

^*Greenebaum Cancer Center of the University of Maryland, Baltimore MD 21201; ^†Department of Medicine, Division of Hematology/Oncology, University of Maryland School of Medicine, Baltimore, MD 21201; ^‡Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201; and ^§Baltimore Veterans Medical Center, Department of Veterans Affairs, Baltimore, MD, 21201

Communicated by David E. Housman, Massachusetts Institute of Technology, Cambridge, MA (received for review March 17, 1998)

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.

Footnotes

↵ ¶ To whom reprint requests should be addressed at: Greenebaum Cancer Center of the University of Maryland, Room 9–015 Bressler Research Building, 655 West Baltimore Street, Baltimore, MD 21201. e-mail: dross{at}umcc01.umcc.ab.umd.edu.
Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF09895).
ABBREVIATIONS:

RT-PCR,

reverse transcription–PCR;

Pgp,

P-glycoprotein;

MRP,

multidrug resistance protein;

ABC,

ATP-binding cassette;

BCRP,

breast cancer resistance protein;

w,

Drosophila white gene