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Contribution of Abcc10 (Mrp7) to in vivo paclitaxel resistance as assessed in Abcc10(-/-) mice.

Cancer research | May 15, 2011

http://www.ncbi.nlm.nih.gov/pubmed/21576088

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.

Pubmed ID: 21576088 RIS Download

Mesh terms: Animals | Antineoplastic Agents, Phytogenic | Bone Marrow | Cytarabine | Drug Resistance, Neoplasm | Female | Fibroblasts | Male | Mice | Mice, Inbred C57BL | Mice, Knockout | Mice, Transgenic | Multidrug Resistance-Associated Proteins | P-Glycoprotein | Paclitaxel | Taxoids | Vincristine

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Associated grants

  • Agency: NCI NIH HHS, Id: 1R15CA143701
  • Agency: NCI NIH HHS, Id: CA06927
  • Agency: NCI NIH HHS, Id: CA073728
  • Agency: NCI NIH HHS, Id: K01 CA120091
  • Agency: NCI NIH HHS, Id: K01 CA120091-04
  • Agency: NCI NIH HHS, Id: K01CA120091
  • Agency: NCI NIH HHS, Id: R15 CA143701
  • Agency: NCI NIH HHS, Id: R15 CA143701-01
  • Agency: NCI NIH HHS, Id: U01 CA073728-04S1

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