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Cancer Prev Res (Phila). 2019 Jun;12(6):343-356. doi: 10.1158/1940-6207.CAPR-18-0401. Epub 2019 Apr 26.

Vitamin D Signaling Suppresses Early Prostate Carcinogenesis in TgAPT121 Mice.

Author information

1
Department of Nutrition Science, Purdue University, West Lafayette, Indiana. fleet@purdue.edu.
2
Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana.
3
Department of Nutrition Science, Purdue University, West Lafayette, Indiana.
4
Division of Medical Oncology, College of Medicine, Columbus, Ohio.
5
Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas-Mérida, Universidad Nacional Autónoma de México, Yucatán, México.
6
School of Medicine, Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
7
The Ohio State University Comprehensive Cancer Center, Columbus, Ohio.

Abstract

We tested whether lifelong modification of vitamin D signaling can alter the progression of early prostate carcinogenesis in studies using mice that develop high-grade prostatic intraepithelial neoplasia that is similar to humans. Two tissue-limited models showed that prostate vitamin D receptor (VDR) loss increased prostate carcinogenesis. In another study, we fed diets with three vitamin D3 levels (inadequate = 25 IU/kg diet, adequate for bone health = 150 IU/kg, or high = 1,000 IU/kg) and two calcium levels (adequate for bone health = 0.5% and high = 1.5%). Dietary vitamin D caused a dose-dependent increase in serum 25-hydroxyvitamin D levels and a reduction in the percentage of mice with adenocarcinoma but did not improve bone mass. In contrast, high calcium suppressed serum 1,25-dihydroxyvitamin D levels and improved bone mass but increased the incidence of adenocarcinoma. Analysis of the VDR cistrome in RWPE1 prostate epithelial cells revealed vitamin D-mediated regulation of multiple cancer-relevant pathways. Our data support the hypothesis that the loss of vitamin D signaling accelerates the early stages of prostate carcinogenesis, and our results suggest that different dietary requirements may be needed to support prostate health or maximize bone mass. SIGNIFICANCE: This work shows that disrupting vitamin D signaling through diet or genetic deletion increases early prostate carcinogenesis through multiple pathways. Higher-diet vitamin D levels are needed for cancer than bone.

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