Reference SummaryZheng W, Int J Cancer 2012 Jan 1;130(1):10-9
Title |
Inactivation of the vitamin D receptor in APC(min/+) mice reveals a critical role for the vitamin D receptor in intestinal tumor growth. |
Authors |
Zheng W; Wong KE; Zhang Z; Dougherty U; Mustafi R; Kong J; Deb DK; Zheng H; Bissonnette M; Li YC |
Journal |
Int J Cancer |
Volume |
130 |
Issue |
1 |
Year |
2012 |
Pages |
10-9 |
Abstract |
Emerging evidence supports an inhibitory role for vitamin D in colorectal carcinogenesis; however, the mechanism remains unclear. The adenomatous polyposis coli (APC)/beta-catenin pathway plays a critical role in colorectal carcinogenesis. The purpose of our study is to explore the interactions of vitamin D and APC/beta-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 beta-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 beta-catenin signaling pathways in intestinal tumorigenesis. |
Links |
J:178583 – MGI References 21328347 – National Library of Medicine/PubMed |
Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
---|---|---|---|---|---|
C57BL/6-ApcMin/+ Vdrtm1Mbd | Intestine - Large Intestine - Colon adenoma | Intestine - Large Intestine - Colon |
observed |
||
C57BL/6J-ApcMin/+ | Intestine - Large Intestine - Colon foci - aberrant crypt (ACF) | Intestine - Large Intestine - Colon |
observed |
||
C57BL/6-ApcMin/+ Vdrtm1Mbd | Intestine - Large Intestine - Colon foci - aberrant crypt (ACF) | Intestine - Large Intestine - Colon |
observed |
||
C57BL/6J-ApcMin/+ | Intestine - Small Intestine adenoma | Intestine - Small Intestine |
observed |
||
C57BL/6-ApcMin/+ Vdrtm1Mbd | Intestine - Small Intestine adenoma | Intestine - Small Intestine |
observed |
||
C57BL/6-ApcMin/+ Vdrtm1Mbd | Intestine - Small Intestine tumor | Intestine - Small Intestine |
observed |
||
C57BL/6J-ApcMin/+ | Intestine adenoma | Intestine |
observed |
||
C57BL/6-ApcMin/+ Vdrtm1Mbd | Intestine adenoma | Intestine |
observed |
||
C57BL/6J-ApcMin/+ | Intestine polyp - adenomatous | Intestine |
observed |
||
C57BL/6-ApcMin/+ Vdrtm1Mbd | Intestine polyp - adenomatous | Intestine |
observed |
||
C57BL/6-ApcMin/+ Vdrtm1Mbd | Intestine tumor | Intestine |
observed |
||
C57BL/6J-ApcMin/+ | Intestine tumor | Intestine |
observed |