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Related Experiment Videos

ABCC10, ABCC11, and ABCC12.

Gary D Kruh1, Yanping Guo, Elizabeth Hopper-Borge

  • 1Medical Science Division, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Gary.Kruh@fccc.edu

Pflugers Archiv : European Journal of Physiology
|July 27, 2006
PubMed
Summary

Multidrug resistance-associated protein (MRP)7 and MRP8 are lipophilic anion transporters that confer resistance to chemotherapy. MRP8 also influences earwax type, while MRP9 function remains unknown.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Multidrug resistance-associated protein (MRP)7, MRP8, and MRP9 are newly identified members of the MRP transporter family.
  • Their physiological roles and functional characteristics are largely uncharacterized, representing an early stage of investigation.

Purpose of the Study:

  • To elucidate the functional characteristics and substrate specificities of MRP7, MRP8, and MRP9.
  • To understand their potential roles in drug resistance and physiological processes.

Main Methods:

  • Functional transport assays were employed to determine the substrate profiles of MRP7 and MRP8.
  • Gene expression analysis and genetic association studies were used to investigate MRP8's role in earwax determination.

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Main Results:

  • MRP7 and MRP8 function as lipophilic anion pumps, conferring resistance to chemotherapeutic agents like docetaxel.
  • MRP8 transports various substrates including cyclic nucleotides, steroid sulfates (DHEAS, E(1)S), glutathione conjugates, and bile acids.
  • A single nucleotide polymorphism in MRP8 is linked to wet vs. dry earwax type.
  • MRP8 exhibits complex substrate interactions, influencing transport rates non-reciprocally.
  • MRP8 functions as a cyclic nucleotide efflux pump, conferring resistance to nucleoside analogs (PMEA, 5FU).
  • The functional characteristics of MRP9 are currently unknown.

Conclusions:

  • MRP7 and MRP8 are functionally characterized as drug efflux pumps with distinct substrate specificities, implicated in chemotherapy resistance.
  • MRP8 plays a role in a human physiological trait (earwax type) and exhibits complex transport kinetics.
  • Further investigation is required to determine the function of MRP9.