Contribution of Abcc10 (Mrp7) to In Vivo Paclitaxel Resistance as Assessed in Abcc10−/− Mice
- 15 May 2011
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 71 (10), 3649-3657
- https://doi.org/10.1158/0008-5472.can-10-3623
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.Other Versions
This publication has 27 references indexed in Scilit:
- Lapatinib and erlotinib are potent reversal agents for MRP7 (ABCC10)-mediated multidrug resistanceBiochemical Pharmacology, 2010
- Imatinib and Nilotinib Reverse Multidrug Resistance in Cancer Cells by Inhibiting the Efflux Activity of the MRP7 (ABCC10)PLOS ONE, 2009
- NEDD9 Promotes Oncogenic Signaling in Mammary Tumor DevelopmentCancer Research, 2009
- Human Multidrug Resistance Protein 7 (ABCC10) Is a Resistance Factor for Nucleoside Analogues and Epothilone BCancer Research, 2008
- MRP7/ABCC10expression is a predictive biomarker for the resistance to paclitaxel in non-small cell lung cancerMolecular Cancer Therapeutics, 2008
- Analysis of the In Vivo Functions of Mrp3Molecular Pharmacology, 2005
- Analysis of the Drug Resistance Profile of Multidrug Resistance Protein 7 (ABCC10)Cancer Research, 2004
- Expression of multidrug resistance-1 protein inversely correlates with paclitaxel response and survival in ovarian cancer patients: a study in serial samplesGynecologic Oncology, 2004
- Mechanisms of Taxol resistance related to microtubulesOncogene, 2003
- Predicting Chemotherapy Response to Paclitaxel-Based Therapy in Advanced Non-Small-Cell Lung Cancer with P-Glycoprotein ExpressionRespiration, 2003