Vitamin D induced regulation of lipids in a mouse model of breast cancer progression using imaging MS and gene array analysis

摘要

The accepted role of vitamin D and its active metabolite 1,25-dihydroxyvitamin D (calcitriol) is in calcium and phosphate homeostasis. Recently, there has been a preponderance of data suggesting that vitamin D is involved in the prevention and progression of malignancy: Calcitriol has anti-proliferative, pro-apoptotic and anti-angiogenic properties. Malignant tissues have altered expression of 1-hydroxylase, 24-hydroxylase and VDR. VDR ablation in mouse models increases carcinogenesis. However, there remains considerable controversy regarding the role of vitamin D in cancer. Despite a number of observational studies that have demonstrated increased risk of colorectal, prostate and breast cancers with low serum vitamin D levels, it is not known if the link is causative or associative. Historically the kidneys were thought to be the site of calcitriol synthesis. It is now known that 1-alpha-hydroxylase is expressed at numerous extra-renal sites so that calcitriol has autocrine and paracrine activity. This helps to explain why vitamin D metabolites have tissue concentrations and activities that correlate poorly with systemic levels. As malignant tissue has altered expression of vitamin D enzymes, serum levels of vitamin D metabolites are poor markers of their tumor concentration and activity. Another approach to exploring the role of vitamin D in cancer would be to look for downstream variations in mRNA and end-products that are dependent on vitamin D levels.