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

Abstract

ABCG2 protein (breast cancer resistance protein, BCRP) is an efflux transmembrane protein involved in the transport of endogenous and exogenous substances, as well as in the development of tumor resistance to chemotherapy. In this work, the effects of sex hormones progesterone, estradiol, and testosterone on the relative content of ABCG2 in Caco-2 cells was evaluated. The role of orphan receptors (farnasoid X receptor (FXR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), and liver X receptor subtype alpha (LXRα) in the effects of sex hormones was also studied. The content of ABCG2 was estimated by the Western blot technique. Hormones were used at concentrations of 1, 10, and 100 μM; exposure duration was 24 h. All hormones at all concentrations caused an increase in the content of ABCG2. Inhibition of PXR and FXR prevented an increase in ABCG2 levels induced by progesterone. Suppression of CAR and PXR partially reduced the expression of ABCG2 caused by estradiol, as compared to exposure to estrogen alone, but still the level of the transporter exceeded the control. Inhibition of PXR and FXR attenuated the inducing effect of testosterone; however, the level of the transporter exceeded the control. Thus, it was shown that all sex hormones at concentrations 1, 10, and 100 μM increased the content of ABCG2. CAR and PXR participated in the action of estradiol, while FXR and PXR participated in the action of testosterone and progesterone.