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

Martin J. Edelman1, Weidong Yang1, Lynne V. Abruzzo1,2, Tammy Krogmann1, Yongming Gao1, Arun K. Rishi1, Douglas D. Ross3,1
1Greenebaum 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
2Hematopathology
3Baltimore VA Medical Center

Tóm tắt

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.

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