title: Breast cancer resistance protein is localized at the plasma membrane in mitoxantrone- and topotecan-resistant cell lines.
abstract: Tumor cells may display a multidrug resistant phenotype by overexpression of ATP-binding cassette transporters such as multidrug resistance (MDRI) 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.
authors.affiliation: Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: G L
authors.initials: GL
authors.lastname: Scheffer
authors.forename: M
authors.initials: M
authors.lastname: Maliepaard
authors.forename: A C
authors.initials: AC
authors.lastname: Pijnenborg
authors.forename: M A
authors.initials: MA
authors.lastname: van Gastelen
authors.forename: M C
authors.initials: MC
authors.lastname: de Jong
authors.forename: A B
authors.initials: AB
authors.lastname: Schroeijers
authors.forename: D M
authors.initials: DM
authors.lastname: van der Kolk
authors.forename: J D
authors.initials: JD
authors.lastname: Allen
authors.forename: D D
authors.initials: DD
authors.lastname: Ross
authors.forename: P
authors.initials: P
authors.lastname: van der Valk
authors.forename: W S
authors.initials: WS
authors.lastname: Dalton
authors.forename: J H
authors.initials: JH
authors.lastname: Schellens
authors.forename: R J
authors.initials: RJ
authors.lastname: Scheper
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000032:analysis*; D000818:Animals; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008942:Mitoxantrone / Q000627:therapeutic use*; D009363:Neoplasm Proteins / Q000032:analysis*; D019772:Topotecan / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D019772:Topotecan; D008942:Mitoxantrone