Characterization of a novel PXR isoform with potential dominant-negative properties

Abstract

Background & Aims The nuclear Pregnane X Receptor (PXR, NR1I2) plays a pivotal role in xenobiotic metabolism. Here, we sought to characterize a new PXR isoform (hereafter called small PXR or sPXR) stemming from alternative transcription starting sites downstream of a CpG Island located near exon 3 of the human PXR gene. Methods Quantitative RT-PCR, western blot, methylation-specific PCR, luciferase reporter assays, electro-mobility shift assays, and stable sPXR overexpression were used to examine sPXR expression and function in hepatocellular cell lines, healthy human liver (n = 99), hepatocellular adenomas (HCA, n = 91) and hepatocellular carcinoma samples (HCC, n = 213). Results Liver sPXR..