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

• Published in: Biology open Vol. 11; no. 7
• Main Authors: Irving, Amy A, Waters, Bayley J, Seeman, Jeremy R, Plum, Lori A, DeLuca, Hector F
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 15-07-2022; The Company of Biologists
• Subjects: Ablation; Animal models; Calciferol; calcium; Colon; Colon cancer; Colorectal cancer; CRISPR; Dextran; Dextrans; Epidemiology; Equator; Inflammation; Intestine; Mutation; Neoplasia; Neoplasms; rat model; Receptors; Small intestine; Sodium sulfate; Tumorigenesis; Tumors; Vitamin D; vitamin d receptor; Vitamin D receptors; Rat model; Colon cancer; Calcium; Vitamin D receptor
• ISSN: 2046-6390; 2046-6390
• DOI: 10.1242/bio.059290

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.