Breast cancer resistance protein is localized at the plasma membrane in mitoxantrone- and topotecan-resistant cell lines

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