Abstract

The breast cancer resistance protein (BCRP; ABCG2) is an ATP-dependent efflux multidrug transporter that belongs to the G family of half-transporters that consist of six transmembrane-spanning domains and must homodimerize to form the active membrane transporter. It is expressed in the apical plasma membrane domain of the small intestine, endothelium, and liver, where it has been shown to play an important role in limiting drug absorption and distribution and in enhancing drug clearance, respectively. BCRP is also expressed in the apical membrane of mammary alveolar epithelia, where it mediates efflux of substrates into milk, and in the placental syncytiotro-phoblasts, where it reduces fetal exposure to these substrates. BCRP substrates include numerous drugs (topotecan, nitrofurantoin, cimetidine) as well as food carcinogens (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) and the vitamins riboflavin and folic acid. BCRP expression is regulated by a number of nuclear transcription factors, including the peroxisome proliferator-activated receptor-γ and Hif-1. This issue of Molecular Pharmacology includes a study (p. 845) now conclusively demonstrating that progesterone acts via the progesterone A and B receptors to regulate BCRP expression in a placental cell line.