| First Author | Fleet JC | Year | 2019 |
| Journal | Cancer Prev Res (Phila) | Volume | 12 |
| Issue | 6 | Pages | 343-356 |
| PubMed ID | 31028080 | Mgi Jnum | J:349085 |
| Mgi Id | MGI:7646065 | Doi | 10.1158/1940-6207.CAPR-18-0401 |
| Citation | Fleet JC, et al. (2019) Vitamin D Signaling Suppresses Early Prostate Carcinogenesis in TgAPT(121) Mice. Cancer Prev Res (Phila) 12(6):343-356 |
| abstractText | 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 D(3) 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. |
