Received for publication December 11, 2007.
Revised December 11, 2007.
Accepted for publication December 17, 2007.

Progesterone acts via Progesterone Receptors A and B to Regulate BCRP Expression (Relates to article by Wang, et al., Fast Forward 27 Nov 2007)

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 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 syncytiotrophblasts, 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, PhIP) and the vitamins riboflavin and folic acid. BCRP expression is regulated by a number of nuclear transcription factors, including the peroxisome proliferator-activated receptor- and Hif-1. This issue of Molecular Pharmacology includes studies now conclusively demonstrating that progesterone acts via the progesterone A and B receptors to regulate BCRP expression in a placental cell line.

Key words: DNA binding sites, Promoter analysis, Organic anion