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Data from Vitamin D Signaling Suppresses Early Prostate Carcinogenesis in TgAPT121 Mice

Data from Vitamin D Signaling Suppresses Early Prostate Carcinogenesis in TgAPT121 Mice

Authors :
Steven K. Clinton
Carsten Carlberg
Antonio Neme
Min Cui
Jennifer M. Thomas-Ahner
Jun-Ge Yu
Colleen Spees
Justin Smolinski
Yan Li
Pavlo L. Kovalenko
James C. Fleet
Publication Year :
2023
Publisher :
American Association for Cancer Research (AACR), 2023.

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.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........d7a60a98b4626016352642446db5a76f
Full Text :
https://doi.org/10.1158/1940-6207.c.6547717.v1