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Vitamin D3 Prevents Calcium-Induced Progression of Early-Stage Prostate Tumors by Counteracting TRPC6 and Calcium Sensing Receptor Upregulation
- Source :
- Cancer Research. 77:355-365
- Publication Year :
- 2017
- Publisher :
- American Association for Cancer Research (AACR), 2017.
-
Abstract
- Active surveillance has emerged as an alternative to immediate treatment for men with low-risk prostate cancer. Accordingly, identification of environmental factors that facilitate progression to more aggressive stages is critical for disease prevention. Although calcium-enriched diets have been speculated to increase prostate cancer risk, their impact on early-stage tumors remains unexplored. In this study, we addressed this issue with a large interventional animal study. Mouse models of fully penetrant and slowly evolving prostate tumorigenesis showed that a high calcium diet dramatically accelerated the progression of prostate intraepithelial neoplasia, by promoting cell proliferation, micro-invasion, tissue inflammation, and expression of acknowledged prostate cancer markers. Strikingly, dietary vitamin D prevented these calcium-triggered tumorigenic effects. Expression profiling and in vitro mechanistic studies showed that stimulation of PC-3 cells with extracellular Ca2+ resulted in an increase in cell proliferation rate, store-operated calcium entry (SOCE) amplitude, cationic channel TRPC6, and calcium sensing receptor (CaSR) expression. Notably, administration of the active vitamin D metabolite calcitriol reversed all these effects. Silencing CaSR or TRPC6 expression in calcium-stimulated PC3 cells decreased cell proliferation and SOCE. Overall, our results demonstrate the protective effects of vitamin D supplementation in blocking the progression of early-stage prostate lesions induced by a calcium-rich diet. Cancer Res; 77(2); 355–65. ©2016 AACR.
- Subjects :
- Male
0301 basic medicine
Cancer Research
medicine.medical_specialty
Calcitriol
chemistry.chemical_element
Biology
Calcium
medicine.disease_cause
Mice
03 medical and health sciences
chemistry.chemical_compound
Prostate cancer
0302 clinical medicine
Prostate
Cell Line, Tumor
Internal medicine
TRPC6 Cation Channel
medicine
Animals
Humans
Cholecalciferol
TRPC Cation Channels
Prostatic Neoplasms
Cancer
medicine.disease
Diet
Up-Regulation
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Oncology
chemistry
030220 oncology & carcinogenesis
Dietary Supplements
Calcium-sensing receptor
Carcinogenesis
Receptors, Calcium-Sensing
medicine.drug
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 77
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....0be953b224070f1a13e5a5a0d80b5e3d