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Vitamin D receptor absence does not enhance intestinal tumorigenesis in Apc(Pirc/+)rats
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277077/ https://www.ncbi.nlm.nih.gov/pubmed/35662320 http://dx.doi.org/10.1242/bio.059290 |
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author | Irving, Amy A. Waters, Bayley J. Seeman, Jeremy R. Plum, Lori A. DeLuca, Hector F. |
author_facet | Irving, Amy A. Waters, Bayley J. Seeman, Jeremy R. Plum, Lori A. DeLuca, Hector F. |
author_sort | Irving, Amy A. |
collection | PubMed |
description | 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)D(3) 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 Apc(Pirc/+) 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. This article has an associated First Person interview with the first author of the paper. |
format | Online Article Text |
id | pubmed-9277077 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-92770772022-07-13 Vitamin D receptor absence does not enhance intestinal tumorigenesis in Apc(Pirc/+)rats Irving, Amy A. Waters, Bayley J. Seeman, Jeremy R. Plum, Lori A. DeLuca, Hector F. Biol Open Research Article 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)D(3) 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 Apc(Pirc/+) 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. This article has an associated First Person interview with the first author of the paper. The Company of Biologists Ltd 2022-07-06 /pmc/articles/PMC9277077/ /pubmed/35662320 http://dx.doi.org/10.1242/bio.059290 Text en © 2022. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Irving, Amy A. Waters, Bayley J. Seeman, Jeremy R. Plum, Lori A. DeLuca, Hector F. Vitamin D receptor absence does not enhance intestinal tumorigenesis in Apc(Pirc/+)rats |
title | Vitamin D receptor absence does not enhance intestinal tumorigenesis in Apc(Pirc/+)rats |
title_full | Vitamin D receptor absence does not enhance intestinal tumorigenesis in Apc(Pirc/+)rats |
title_fullStr | Vitamin D receptor absence does not enhance intestinal tumorigenesis in Apc(Pirc/+)rats |
title_full_unstemmed | Vitamin D receptor absence does not enhance intestinal tumorigenesis in Apc(Pirc/+)rats |
title_short | Vitamin D receptor absence does not enhance intestinal tumorigenesis in Apc(Pirc/+)rats |
title_sort | vitamin d receptor absence does not enhance intestinal tumorigenesis in apc(pirc/+)rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277077/ https://www.ncbi.nlm.nih.gov/pubmed/35662320 http://dx.doi.org/10.1242/bio.059290 |
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