title: The 315-316 deletion determines the BXP-21 antibody epitope but has no effect on the function of wild type ABCG2 or the Q141K variant.
abstract: ABCG2 is a half-transporter initially described in multidrug-resistant cancer cells and lately identified as an important factor in the pharmacokinetics of its substrates. Q141K is by far the most intensively studied single nucleotide polymorphism of ABCG2 with potential clinical relevance. Here we used stably transfected HEK cells to study the Q141K polymorphism together with the deletion of amino acids 315-316, which were recently reported to coexist in two cancer cell lines (A549 and SK-OV-3). Functional studies confirmed our previous report that when normalized to surface expression, Q141K has impaired transport of mitoxantrone. This result was extended to include the ABCG2-specific substrate pheophorbide a. While we found no functional consequence of deleting amino acids 315 and 316, we did find that the deletion mutant is no longer recognized by the BXP-21 antibody. We conclude that amino acids 315 and 316 form part of the epitope for the BXP-21 antibody.
authors.affiliation: Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Orsolya
authors.initials: O
authors.lastname: Polgar
authors.forename: John F
authors.initials: JF
authors.lastname: Deeken
authors.forename: Lilangi S
authors.initials: LS
authors.lastname: Ediriwickrema
authors.forename: Akina
authors.initials: A
authors.lastname: Tamaki
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Robert W
authors.initials: RW
authors.lastname: Robey
authors.forename: Susan E
authors.initials: SE
authors.lastname: Bates
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000596:Amino Acids / Q000235:genetics; D000911:Antibodies, Monoclonal / Q000276:immunology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D019008:Drug Resistance, Neoplasm; D000939:Epitopes / Q000235:genetics* / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D014162:Transfection
chemical_list: D018528:ATP-Binding Cassette Transporters; D000596:Amino Acids; D000911:Antibodies, Monoclonal; D000939:Epitopes