Vitamin D Signaling Suppresses Early Prostate Carcinogenesis in TgAPT121 Mice
Self archived versionfinal draft
MetadataShow full item record
CitationFleet, JC. Kovalenko, PL. Li, Y. Smolinski, J. Spees, C. Yu, JG. Thomas-Ahner, JM. Cui, M. Neme, A. Carlberg, C. Clinton, SK. (2019). Vitamin D Signaling Suppresses Early Prostate Carcinogenesis in TgAPT121 Mice. Cancer prevention research, 12 (6) , 343-356. 10.1158/1940-6207.CAPR-18-0401.
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.
Subjectsdiet calcium vitamin D receptor prevention carcinogenesis
Link to the original itemhttp://dx.doi.org/10.1158/1940-6207.CAPR-18-0401
PublisherAmerican Association for Cancer Research (AACR)
- Terveystieteiden tiedekunta