Up-regulation of CAR expression through Elk-1 in HepG2 and SW480 cells by serum starvation stress

Constitutive androstane receptor ( CAR) is a transcription factor regulating the expression of several genes related to drug metabolism. CAR expression was elevated in human HepG2 and SW480 cells by serum starvation. From reporter gene assays, mutagenesis, RNA interference, and chromatin immunoprecipitation assays, we identified the serum response element at -142/-139 in the CAR gene transactivated by Elk-1. Whereas treatment with U0126 (ERK inhibitor) enhanced CAR expression, SP600125 (stress-activated protein kinase inhibitor, SAPK) suppressed the phosphorylation of Elk-1 caused by serum-starvation stress and the elevation of CAR mRNA, suggesting that CAR expression may be mediated by phosphorylated Elk-1 via the SAPK signaling pathway. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.