The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane.
The Breast Cancer Resistance Protein (BCRP/ABCG2) is a transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. This transporter is highly expressed in many tissues; however, in human kidney, only the mRNA was found in contrast to the mouse kidney, where the transporter is abundant. In bcrp/abcg2((-/-)) mice, the expression of two sterol transporter genes, abcg5 and abcg8, was strongly increased in the kidney, perhaps as a compensatory mechanism to upregulate efflux. We found using immunohistochemical analysis clear localization of BCRP/ABCG2 to the proximal tubule brush border membrane of the human kidney comparable to that of other ABC transporters such as P-glycoprotein/ABCB1, MRP2/ABCC2, and MRP4/ABCC4. Hoechst 33342 dye efflux from primary human proximal tubule cells was significantly reduced by the BCRP/ABCG2 inhibitors fumitremorgin C and nelfinavir. Our study shows that in addition to other apical ABC transporters, BCRP/ABCG2 may be important in renal drug excretion.
Huls
M
M
Department of Pharmacology and Toxicology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Brown
C D A
CD
Windass
A S
AS
Sayer
R
R
van den Heuvel
J J M W
JJ
Heemskerk
S
S
Russel
F G M
FG
Masereeuw
R
R
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D000089762:Multidrug Resistance-Associated Protein 2; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats
C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000089762:Multidrug Resistance-Associated Protein 2; D009363:Neoplasm Proteins; D012333:RNA, Messenger