Influence of Sex Hormones on the ABCG2 Transport Protein in Caco-2 Cells

Abstract

Protein ABCG2 (BCRP, breast cancer resistance protein) is an efflux transmembrane protein involved in the transport of endo- and exogenous substances, as well as in the development of tumor resistance to chemotherapy. In this work, the influence of sex hormones progesterone, estradiol, and testosterone on the relative amount of ABCG2 in Caco-2 cells was studied, as well as the role of orphan receptors (farnazoid X receptor (FXR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), hepatic X receptor subtype alpha (LXRa)) in this process. The amount of ABCG2 was assessed by Western blot. Hormones were used at concentrations of 1, 10, and 100 µM, exposure time was 24 h. All hormones at all concentrations caused an increase in the amount of ABCG2. Inhibition of PXR and FXR prevented the increase in ABCG2 under the action of progesterone. Suppression of CAR and PXR reduced ABCG2 levels with estradiol compared with estrogen exposure alone, but still the transporter level was higher than in controls. Inhibition of PXR and FXR reduced the effect of testosterone; however, the level of the transporter exceeded the control values. Thus, our study showed that all sex hormones at all concentrations used increased the amount of ABCG-2, that CAR and PXR are involved in the implementation of the action of estradiol, and that FXR and PXR are involved in the implementation of the effects of testosterone and progesterone.