Quantitative assessment of breast cancer resistance protein during pregnancy in rabbits

Abstract

Breast cancer resistance protein (BCRP,ABCG2) is an efflux transporter protein that transports various substrates from the cell to the extracellular space or organ cavities. The aim of this study was a complex assessment of the amount of BCRP during pregnancy in rabbits. The amount of BCRP in samples of the rabbit jejunum, liver, kidney, cerebral cortex, and placenta was determined by enzyme immunoassay, and in human hepatocellular carcinoma (HepG2) cells by the Western blot. To study the mechanisms involved in control of the dynamic BCRP levels during pregnancy, serum concentrations of sex hormones were investigated by radioimmunoassay and relative amounts of constitutive androstane receptor (CAR) and pregnane X receptor (PXR) in these organs were evaluated using the Western blot method. The putative role of CAR and PXR in regulation of the BCRP level by progesterone was evaluated in vitro experiments on HepG2 cells. It was found that amount of BCRP in the jejunum of pregnant rabbits was higher than in the placenta, liver, kidneys, and cerebral cortex. An increase in the amount of BCRP in the liver of rabbits was noted on the 21st day of pregnancy and a tendency to the increase was also detected on the 28th day; in the kidney and cerebral cortex increased BCRP levels were detected on the 28th day and 14th day of pregnancy, respectively, as compared with non-pregnant females. In vitro experiments with HepG2 cells have shown that the increase in the BCRP level is determined by the activating effect of progesterone on PXR.