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

FEBS Lett. 2009 Mar 4;583(5):885-9. doi: 10.1016/j.febslet.2009.01.051. Epub 2009 Feb 6.

Abstract

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.

MeSH terms

  • 5' Flanking Region / genetics
  • Anthracenes / pharmacology
  • Base Sequence
  • Cell Line, Tumor
  • Culture Media, Serum-Free
  • Humans
  • Molecular Sequence Data
  • Phosphorylation / drug effects
  • Protein Binding
  • RNA, Messenger / genetics
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Signal Transduction
  • Stress, Physiological*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation / genetics
  • Up-Regulation*
  • ets-Domain Protein Elk-1 / genetics
  • ets-Domain Protein Elk-1 / metabolism*

Substances

  • Anthracenes
  • Culture Media, Serum-Free
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • pyrazolanthrone
  • constitutive androstane receptor