American Association for Cancer Research
Browse

Supplementary Figure 1 from Contribution of Abcc10 (Mrp7) to In Vivo Paclitaxel Resistance as Assessed in Abcc10−/− Mice

Download (112.04 kB)
journal contribution
posted on 2023-03-30, 20:20 authored by Elizabeth A. Hopper-Borge, Timothy Churchill, Chelsy Paulose, Emmanuelle Nicolas, Joely D. Jacobs, Olivia Ngo, Yehong Kuang, Alex Grinberg, Heiner Westphal, Zhe-Sheng Chen, Andres J. Klein-Szanto, Martin G. Belinsky, Gary D. Kruh
Supplementary Figure 1 from Contribution of Abcc10 (Mrp7) to In Vivo Paclitaxel Resistance as Assessed in Abcc10−/− Mice

History

ARTICLE ABSTRACT

Recently, we reported that the ATP-binding cassette transporter 10 (ABCC10), also known as multidrug resistance protein 7 (MRP7), is able to confer resistance to a variety of anticancer agents, including taxanes. However, the in vivo functions of the pump have not been determined to any extent. In this study, we generated and analyzed Abcc10−/− mice to investigate the ability of Abcc10 to function as an endogenous resistance factor. Mouse embryo fibroblasts derived from Abcc10−/− mice were hypersensitive to docetaxel, paclitaxel, vincristine, and cytarabine (Ara-C) and exhibited increased cellular drug accumulation, relative to wild-type controls. Abcc10−/− null mice treated with paclitaxel exhibited increased lethality associated with neutropenia and marked bone marrow toxicity. In addition, toxicity in spleen and thymus was evident. These findings indicate that Abcc10 is dispensable for health and viability and that it is an endogenous resistance factor for taxanes, other natural product agents, and nucleoside analogues. This is the first demonstration that an ATP-binding cassette transporter other than P-glycoprotein can affect in vivo tissue sensitivity toward taxanes. Cancer Res; 71(10); 3649–57. ©2011 AACR.

Usage metrics

    Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC