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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.

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


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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