Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis.
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Janvilisri T, Venter H, Shahi S, Reuter G, Balakrishnan L, van Veen HW
Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis.
J Biol Chem. 2003 Jun 6;278(23):20645-51. Epub 2003 Mar 28.
- PubMed ID
- 12668685 [ View in PubMed]
- Abstract
The human breast cancer resistance protein (BCRP, also know as ABCG2, MXR, or ABCP) is one of the more recently discovered ATP-binding cassette (ABC) transporters that confer resistance on cancer cells by mediating multidrug efflux. In the present study, we have obtained functional expression of human BCRP in the Gram-positive bacterium Lactococcus lactis. BCRP expression conferred multidrug resistance on the lactococcal cells, which was based on ATP-dependent drug extrusion. BCRP-mediated ATPase and drug transport activities were inhibited by the BCRP-specific modulator fumitremorgin C. To our knowledge these data represent the first example of the functional expression of a mammalian ABC half-transporter in bacteria. Although members of the ABCG subfamily (such as ABCG1 and ABCG5/8) have been implicated in the transport of sterols, such a role has not yet been established for BCRP. Interestingly, the BCRP-associated ATPase activity in L. lactis was significantly stimulated by (i) sterols including cholesterol and estradiol, (ii) natural steroids such as progesterone and testosterone, and (iii) the anti-estrogen anticancer drug tamoxifen. In addition, BCRP mediated the efflux of [3H]estradiol from lactococcal cells. Our findings suggest that BCRP may play a role in the transport of sterols in human, in addition to its ability to transport multiple drugs and toxins.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Cholesterol ATP-binding cassette sub-family G member 2 Protein Humans UnknownInducerDetails Daunorubicin ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateDetails Sumatriptan ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateDetails Tamoxifen ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateDetails Testosterone ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateDetails Testosterone cypionate ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateDetails Testosterone enanthate ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateDetails Testosterone undecanoate ATP-binding cassette sub-family G member 2 Protein Humans UnknownSubstrateDetails