The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane

Kidney Int. 2008 Jan;73(2):220-5. doi: 10.1038/sj.ki.5002645. Epub 2007 Oct 31.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / analysis
  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / physiology
  • Animals
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Humans
  • Immunohistochemistry
  • Kidney Tubules, Proximal / chemistry
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / metabolism*
  • Mice
  • Multidrug Resistance-Associated Protein 2
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / physiology
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Rats

Substances

  • ABCC2 protein, human
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Multidrug Resistance-Associated Protein 2
  • Neoplasm Proteins
  • RNA, Messenger