Cancer Research AACR Conference on Molecular Diagnostics - 2008 Susan G. Komen for the Cure-AACR Outstanding Investigator Award for Breast Cancer Research
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[Cancer Research 60, 2589-2593, May 15, 2000]
© 2000 American Association for Cancer Research

Advances in Brief

Breast Cancer Resistance Protein Is Localized at the Plasma Membrane in Mitoxantrone- and Topotecan-resistant Cell Lines1

George L. Scheffer, Marc Maliepaard, Adriana C. L. M. Pijnenborg, Margôt A. van Gastelen, Mariska C. de Jong, Anouk B. Schroeijers, Dorina M. van der Kolk, John D. Allen, Douglas D. Ross, Paul van der Valk, William S. Dalton, Jan H. M. Schellens and Rik J. Scheper2

Department of Pathology, Free University Hospital, 1081 HV Amsterdam, the Netherlands [G. L. S., A. C. L. M. P., M. C. d. J., A. B. S., P. v. d. V., R. J. S.]; Division of Experimental Therapy, The Netherlands Cancer Institute, 1066CX Amsterdam, the Netherlands [M. M., M. A. v. G., J. D. A., J. H. M. S.]; Department of Hematology and Medical Oncology, Academic Hospital Groningen, 9700RB Groningen, the Netherlands [D. M. v. d. K]; Department of Medicine, Division of Hematology/Oncology, Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland 21201 [D. D. R.]; and Department of Biochemistry, Pharmacology, and Internal Medicine, H. Lee Moffitt Cancer Center, University of South Florida, Tampa, Florida 33612 [W. S. D.]

Tumor cells may display a multidrug resistant phenotype by overexpression of ATP-binding cassette transporters such as multidrug resistance (MDR1) P-glycoprotein, multidrug resistance protein 1 (MRP1), and breast cancer resistance protein (BCRP). The presence of BCRP has thus far been reported solely using mRNA data. In this study, we describe a BCRP-specific monoclonal antibody, BXP-34, obtained from mice, immunized with mitoxantrone-resistant, BCRP mRNA-positive MCF-7 MR human breast cancer cells. BCRP was detected in BCRP-transfected cells and in several mitoxantrone- and topotecan-selected tumor cell sublines. Pronounced staining of the cell membranes showed that the transporter is mainly present at the plasma membrane. In a panel of human tumors, including primary tumors as well as drug-treated breast cancer and acute myeloid leukemia samples, BCRP was low or undetectable. Extended studies will be required to analyze the possible contribution of BCRP to clinical multidrug resistance.




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