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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

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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.

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Acknowledgments

The authors would like to thank Elizabeth Finley for help with the flow cytometry experiments.

This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

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Authors and Affiliations

  1. Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD, 20892, USA

    Orsolya Polgar, Lilangi S. Ediriwickrema, Akina Tamaki, Robert W. Robey & Susan E. Bates

  2. Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, 20007, USA

    John F. Deeken

  3. Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Bethesda, MD, 20892, USA

    Seth M. Steinberg

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  1. Orsolya Polgar
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Correspondence to Susan E. Bates.

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Polgar, O., Deeken, J.F., Ediriwickrema, L.S. et al. 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. Mol Cell Biochem 322, 63–71 (2009). https://doi.org/10.1007/s11010-008-9940-0

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  • DOI: https://doi.org/10.1007/s11010-008-9940-0

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