Liganded VDR induces CYP3A4 in small intestinal and colon cancer cells via DR3 and ER6 vitamin D responsive elements

Paul D. Thompson, Peter W. Jurutka, G. Kerr Whitfield, Sandy M. Myskowski, Kristina R. Eichhorst, Carlos Encinas Dominguez, Carol A. Haussler, Mark R. Haussler

Research output: Contribution to journalArticlepeer-review

134 Scopus citations


The nuclear vitamin D receptor (VDR) mediates the effects of 1, 25-dihydroxyvitamin D3 1, 25D3 to alter intestinal gene transcription and promote calcium absorption. Because 1, 25D3 also exerts anti-cancer effects, we examined the efficacy of 1, 25D3 to induce cytochrome P450 (CYP) enzymes. Exposure of human colorectal adenocarcinoma cells (HT-29) to 108 M 1, 25D3 resulted in ≥3-fold induction of CYP3A4 mRNA and protein as assessed by RT-PCR and Western blotting, respectively. Six vitamin D responsive element (VDRE)-like sequences in the promoter region of the CYP3A4 gene were then individually tested for their ability to enhance transcription. A canonical DR3-type element in the distal region of the promoter(-7719-GGGTCAgcaAGTTCA-7733), and a proximal, non-classical everted repeat with a spacer of 6 bp (ER6; -169-TGAACTcaaaggAGGTCA-152) were identified as functional VDREs in this CYP gene. These data suggest that 1, 25D3-dependent, VDR-mediated induction of CYP3A4 may constitute a chemoprotective mechanism for detoxification of enteric xenobiotics and carcinogens.

Original languageEnglish (US)
Pages (from-to)730-738
Number of pages9
JournalBiochemical and Biophysical Research Communications
Issue number5
StatePublished - 2002


  • 1, 25-Dihydroxyvitamin D
  • Carcinogens
  • Chemoprevention
  • Cytochrome P450
  • Detoxification
  • Enterocytes
  • Nuclear vitamin D receptor
  • Pregnane X receptor
  • Retinoid X receptor
  • Xenobiotics

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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