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Inactivation of the vitamin D receptor in APCmin/+ mice reveals a critical role for the vitamin D receptor in intestinal tumor growth

Inactivation of the vitamin D receptor in APCmin/+ mice reveals a critical role for the vitamin D... 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. APCmin/+ mice with genetic inactivation of the vitamin D receptor (VDR) were generated through breeding. Intestinal tumorigenesis was compared between APCmin/+ and APCmin/+VDR−/− mice at different ages. No differences were seen in the number of small intestinal and colonic tumors between APCmin/+ and APCmin/+VDR−/− mice aged 3, 4, 6 and 7 months. The size of the tumors, however, was significantly increased in APCmin/+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 APCmin/+VDR−/− tumors compared to APCmin/+ tumors. These observations suggest that VDR signaling inhibits tumor growth rather than tumor initiation in the intestine. Thus, the increased tumor burden in APCmin/+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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Journal of Cancer Wiley

Inactivation of the vitamin D receptor in APCmin/+ mice reveals a critical role for the vitamin D receptor in intestinal tumor growth

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References (53)

Publisher
Wiley
Copyright
Copyright © 2012 Wiley Subscription Services
ISSN
0020-7136
eISSN
1097-0215
DOI
10.1002/ijc.25992
pmid
21328347
Publisher site
See Article on Publisher Site

Abstract

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. APCmin/+ mice with genetic inactivation of the vitamin D receptor (VDR) were generated through breeding. Intestinal tumorigenesis was compared between APCmin/+ and APCmin/+VDR−/− mice at different ages. No differences were seen in the number of small intestinal and colonic tumors between APCmin/+ and APCmin/+VDR−/− mice aged 3, 4, 6 and 7 months. The size of the tumors, however, was significantly increased in APCmin/+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 APCmin/+VDR−/− tumors compared to APCmin/+ tumors. These observations suggest that VDR signaling inhibits tumor growth rather than tumor initiation in the intestine. Thus, the increased tumor burden in APCmin/+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.

Journal

International Journal of Cancer – Wiley

Published: Jan 1, 2012

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