Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6).
Article Details
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Belinsky MG, Chen ZS, Shchaveleva I, Zeng H, Kruh GD
Characterization of the drug resistance and transport properties of multidrug resistance protein 6 (MRP6, ABCC6).
Cancer Res. 2002 Nov 1;62(21):6172-7.
- PubMed ID
- 12414644 [ View in PubMed]
- Abstract
Mutations in human multidrug resistance protein 6 (MRP6, ABCC6), a member of the MRP family of drug efflux pumps, are the genetic basis of Pseudoxanthoma elasticum, a disease that affects elastin fibers in the skin, retina, and blood vessels. However, little is known about the functional characteristics of the protein, including its potential activity as a resistance factor for anticancer agents. Here, we report the results of investigations of the in vitro transport properties and drug resistance activity of MRP6. Using membrane vesicles prepared from Chinese hamster ovary cells transfected with MRP6 expression vector, it is shown that expression of MRP6 is specifically associated with the MgATP-dependent transport of the glutathione S-conjugates leukotriene C(4) and S-(2, 4-dinitrophenyl)glutathione and the cyclopentapeptide BQ123 but not glucuronate conjugates such as 17beta-estradiol 17-(beta-D-glucuronide). Analysis of the drug sensitivity of MRP6-transfected cells revealed low levels of resistance to several natural product agents, including etoposide, teniposide, doxorubicin, and daunorubicin. These results indicate that MRP6 is a glutathione conjugate pump that is able to confer low levels of resistance to certain anticancer agents.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Cisplatin Multidrug resistance-associated protein 6 Protein Humans UnknownSubstrateDetails Dactinomycin Multidrug resistance-associated protein 6 Protein Humans UnknownSubstrateDetails Daunorubicin Multidrug resistance-associated protein 6 Protein Humans UnknownSubstrateDetails Doxorubicin Multidrug resistance-associated protein 6 Protein Humans UnknownSubstrateInhibitorDetails Etoposide Multidrug resistance-associated protein 6 Protein Humans UnknownSubstrateInhibitorDetails Teniposide Multidrug resistance-associated protein 6 Protein Humans UnknownSubstrateDetails