Vitamin D receptor absence does not enhance intestinal tumorigenesis in ApcPirc/+rats

Abstract

Epidemiological observations have prompted some to posit that elevated circulating vitamin D is responsible for reduced colon cancer in individuals residing near the equator. We have previously demonstrated that vitamin D has no effect on colon cancer in two rodent models of intestinal tumorigenesis. We have now extended this line of inquiry to ask whether ablation of vitamin D receptor (VDR) affects tumorigenesis. A VDR null rat was developed using Cas9-CRISPR technology, which allowed us to investigate whether 1,25(OH)D3 signaling through its receptor plays a role in intestinal tumorigenesis. Loss of VDR expression alone did not induce tumorigenesis, even in animals exposed to the inflammatory agent dextran sodium sulfate. These VDR−/- rats were then crossed with ApcPirc/+ rats, which are predisposed to the development of intestinal neoplasms. In combination with the Pirc/+ mutation, VDR loss did not enhance tumor multiplicity, growth, or progression in the colon or small intestine. This study demonstrates that the vitamin D receptor does not impact tumor development, and strongly supports previous findings that vitamin D itself does not play a role in colon cancer development or progression. Alternative explanations are needed for the original latitude hypothesis, as well as observational data in humans.

New Insights into Bile Acids Related Signaling Pathways in the Onset of Colorectal Cancer

“…Irving et al demonstrated in both rat and mouse models of colon cancer that vitamin D supplementation does not protect against intestinal tumor development; it instead enhances tumorigenesis in the colon of the rat [ 145 , 146 ]. Moreover, the same group recently reported that loss of VDR expression alone did not induce tumorigenesis, even in animals exposed to the carcinogenic molecule sodium dextran sulfate [ 147 ]. Moreover, in Apc Pirc/+ rats, VDR loss did not enhance tumor multiplicity, growth, or progression in the colon, thus supporting previous findings that vitamin D itself does not play a role in colon cancer development or progression.…”

Application of CRISPR-Cas9 gene editing technology in basic research, diagnosis and treatment of colon cancer

“…found that vitamin D did not affect the development of colon cancer. Through the gene knockout vitamin D receptor (VDR), it was found that the loss of VDR expression did not promote the occurrence of the tumor, and did not affect the proliferation and progression of the tumor ( 29 ).…”

First person – Amy Irving

“… ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping early-career researchers promote themselves alongside their papers. Amy Irving is first author on ‘ Vitamin D receptor absence does not enhance intestinal tumorigenesis in Apc Pirc/+ rats ’, published in BiO. Amy is a research scientist in the lab of Hector DeLuca at the University of Wisconsin-Madison, USA, investigating the individual contributions of sunlight, vitamin D, calcium, and other pathway players on diseases with a location association paradigm, specifically colon cancer and multiple sclerosis.…”