Expression of VDR and CYP24A1 mRNA in human tumors

Cancer Chemother Pharmacol. 2006 Jan;57(2):234-40. doi: 10.1007/s00280-005-0059-7. Epub 2005 Sep 23.


1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and its analogues have been shown to inhibit proliferation of human cancer cells mediated by vitamin D receptor (VDR). The over-expression of 25-hydroxyvitamin D-24-hydroxylase (CYP24A1), an enzyme involved in the metabolism of 1,25(OH)2D3 and its analogues, is associated with poor prognosis of some human cancers. In this study, we employed real-time reverse transcription PCR to examine the expression of VDR and CYP24A1 mRNA in a cohort of human breast, lung, colon and ovary tumor samples. We found that CYP24A1 mRNA was significantly up-regulated in colon, ovary and lung tumors, but down-regulated in breast tumor relative to the analogous normal tissues. As a comparison, VDR mRNA was modestly down-regulated in colon, breast and lung tumors, but highly up-regulated in ovarian tumors. Treatment of two breast cancer cell lines, SW-620 and MCF-7, and one colon cancer cell line, HT-29, by 1,25(OH)2D3 for 48 h profoundly stimulated CYP24A1 mRNA expression (EC50=0.6, 0.8 and 29.5 nM in SW-620, HT-29 and MCF-7, respectively), but did not significantly affect VDR mRNA expression. Growth as assessed by DNA synthesis was modestly arrested by 1,25(OH)2D3 after 72 h of incubation, but was not altered after a 5-day incubation period. These data suggest that the VDR signaling pathway may be compromised via the modulation of CYP24A1 and VDR in human tumors.

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Calcitriol / metabolism
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology*
  • DNA / biosynthesis
  • Down-Regulation
  • Female
  • Gene Expression Profiling
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology*
  • RNA, Messenger / biosynthesis
  • Receptors, Calcitriol / biosynthesis*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Steroid Hydroxylases / biosynthesis*
  • Steroid Hydroxylases / metabolism
  • Tumor Cells, Cultured
  • Vitamin D3 24-Hydroxylase


  • RNA, Messenger
  • Receptors, Calcitriol
  • DNA
  • Steroid Hydroxylases
  • CYP24A1 protein, human
  • Vitamin D3 24-Hydroxylase
  • Calcitriol