Rare variants in the ABCG2 promoter modulate in vivo activity

Abstract

ABCG2 encodes the breast cancer resistance protein (BCRP), an rs139256004, and rs59370292) decreased the promoter activity by efflux membrane transporter important in the detoxification of 25%-50% in at least three of the four cell lines. The activity of these xenobiotics. In the present study, the basal activity of the ABCG2 four variants was also examined in vivo using the hydrodynamic tail promoter in liver, kidney, intestine, and breast cell lines was examined vein assay, and two single nucleotide polymorphisms (rs76656413 and using luciferase reporter assays. The promoter activities of reference rs59370292) significantly decreased in vivo liver promoter activity by and variant ABCG2 sequences were compared in human hepato-50%-80%. Electrophoretic mobility shift assays confirmed a reduc-cellular carcinoma cell (HepG2), human embryonic kidney cell tion in nuclear protein binding to the rs59370292 variant probe, (HEK293T), human colorectal carcinoma cell (HCT116), and human whereas the rs76656413 probe had a shift in transcription factor breast adenocarcinoma cell (MCF-7) lines. The ABCG2 promoter binding specificity. Although both rs59370292 and rs76656413 are rare activity was strongest in the kidney and intestine cell lines. Four variants in all populations, they could contribute to patient-level variants in the basal ABCG2 promoter (rs76656413, rs66664036, variation in ABCG2 expression in the kidney, liver, and intestine.