Inactivation of the vitamin D receptor in APC(min/+) mice reveals a critical role for the vitamin D receptor in intestinal tumor growth

Int J Cancer. 2012 Jan 1;130(1):10-9. doi: 10.1002/ijc.25992. Epub 2011 Apr 20.


Emerging evidence supports an inhibitory role for vitamin D in colorectal carcinogenesis; however, the mechanism remains unclear. The adenomatous polyposis coli (APC)/β-catenin pathway plays a critical role in colorectal carcinogenesis. The purpose of our study is to explore the interactions of vitamin D and APC/β-catenin pathways in intestinal tumor development. APC(min/+) mice with genetic inactivation of the vitamin D receptor (VDR) were generated through breeding. Intestinal tumorigenesis was compared between APC(min/+) and APC(min/+) VDR(-/-) mice at different ages. No differences were seen in the number of small intestinal and colonic tumors between APC(min/+) and APC(min/+) VDR(-/-) mice aged 3, 4, 6 and 7 months. The size of the tumors, however, was significantly increased in APC(min/+) VDR(-/-) mice in all age groups. Immunostaining showed significant increases in β-catenin, cyclin D1, phosphorylated Stat-3 and MSH-2 levels and decreases in Stat-1 in APC(min/+) VDR(-/-) tumors compared to APC(min/+) tumors. These observations suggest that VDR signaling inhibits tumor growth rather than tumor initiation in the intestine. Thus, the increased tumor burden in APC(min/+) VDR(-/-) mice is likely due to the loss of the growth-inhibiting effect of VDR. This study provides strong evidence for the in vivo relevance of the interaction demonstrated in vitro between the vitamin D and β-catenin signaling pathways in intestinal tumorigenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Genes, APC / physiology*
  • Immunoenzyme Techniques
  • Immunoprecipitation
  • Intestinal Neoplasms / etiology*
  • Intestinal Neoplasms / metabolism
  • Intestinal Neoplasms / pathology*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / genetics
  • Receptors, Calcitriol / antagonists & inhibitors
  • Receptors, Calcitriol / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • beta Catenin / metabolism


  • RNA, Messenger
  • Receptors, Calcitriol
  • beta Catenin