Analysis of the Drug Resistance Profile of Multidrug Resistance Protein 7 (ABCC10)

These results indicate that MRP7, unlike other multidrug resistance protein, is a resistance factor for taxanes

Elizabeth Hopper-Borge

2005

Scholarcy highlights

  • The multidrug resistance protein family is composed of nine related ABC transporters, many of whose substrate selectivities and drug resistance capabilities have been determined to at least some extent. Members of this family can be classified according to whether or not they possess a third membrane-spanning domain. This topological feature is present in MRP1, MRP2, MRP3, MRP6, and MRP7, whereas it is absent in MRP4, MRP5, MRP8, and MRP9
  • Ectopic expression of MRP7 in the two MRP7-transfected clones is indicated by the intensely immunoreactive bands that migrated with an apparent Mr ϳ171,000, but were not present in membranes prepared from the control cells
  • The present study shows that MRP7 is able to confer resistance to natural product anticancer agents, including taxanes, Vinca alkaloids, and possibly anthracyclines
  • This drug resistance profile suggests that natural product drugs are substrates of MRP7, and in combination with our previous determination that MRP7 is competent in the ATPdependent transport of 17␤-estradiol 17-(␤-D-glucuronide), indicates that MRP7 is an amphipathic anion transporter whose substrate selectivity extends to uncharged or mildly cationic lipophilic compounds
  • This conclusion is in accord with our previous determination that MRP7mediated transport of 17␤-estradiol 17-(␤-D-glucuronide) is susceptible to inhibition by natural product anticancer agents
  • In addition to protein expression studies in normal tissues and cancers, it will be of interest to determine whether MRP7 assumes apical or basolateral subcellular localization in polarized epithelial cells

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