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
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..View full abstract
This work was supported by grants obtained from the Ligue contre le Cancer, the Association pour la Recherche contre le Cancer (ARC) and the University of Montpellier 1.