Journal article

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

Cyril Breuker, Chris Planque, Fatemeh Rajabi, Jean-Charles Nault, Gabrielle Couchy, Jessica Zucman-Rossi, Alexandre Evrard, Jovana Kantar, Eric Chevet, Paulette Bioulac-Sage, Jeanne Ramos, Eric Assenat, Dominique Joubert, Julie Pannequin, Frederic Hollande, Jean Marc Pascussi

Journal of Hepatology | ELSEVIER | Published : 2014

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 mR..

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University of Melbourne Researchers