A comparison of vitamin D activity in paired non-malignant and malignant human breast tissues

• Published in: Molecular and cellular endocrinology 2012-10, Vol.362 (1-2), p.202-210
• Main Authors: Suetani, Rachel J., Ho, Kristen, Jindal, Shalini, Manavis, Jim, Neilsen, Paul M., Pishas, Kathleen I., Rippy, Elisabeth, Bochner, Melissa, Kollias, James, Gill, P. Grantley, Morris, Howard A., Callen, David F.
• Format: Article
• Language: English
• Subjects: 1,25-Dihydroxyvitamin D; 25-Hydroxyvitamin D; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - genetics; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - metabolism; Breast; Breast cancer; breast neoplasms; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Calcifediol - pharmacology; Calcifediol - physiology; Calcitriol - pharmacology; Calcitriol - physiology; Cell Proliferation; cultured cells; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; Endocrinology; epidemiological studies; Epidemiology; Ex vivo breast tissue; Female; Gene Expression; Human; Humans; Imidazoles - pharmacology; Ki-67 Antigen - metabolism; Links; messenger RNA; Metabolites; patients; Piperazines - pharmacology; protein synthesis; Proteins; Proto-Oncogene Proteins c-mdm2 - antagonists & inhibitors; Receptors, Calcitriol - metabolism; risk; Steroid Hydroxylases - genetics; Steroid Hydroxylases - metabolism; Tissue Culture Techniques; tissues; Up-Regulation; vitamin D; Vitamin D3 24-Hydroxylase; vitamin status; Vitamins
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2012.06.022

► We used an ex vivo human tissue system to look at vitamin D effects on breast tissue. ► We compared the effects of 25D and 1,25D on paired malignant and non-malignant breast tissues. ► CYP24A1 mRNA levels were significantly upregulated in all tissue types after treatment. ► Differential tissue proliferation responses were seen to 25D and 1,25D in some malignant tissues. Links between a low vitamin D status and an increased risk of breast cancer have been observed in epidemiological studies. These links have been investigated in human tissue homogenates and cultured cell lines. We have used non-malignant, malignant and normal reduction mammoplasty breast tissues to investigate the biological and metabolic consequences of the application of vitamin D to intact ex vivo human breast tissue. Tissues were exposed to 1α,25(OH)2D3 (1,25D; active metabolite) and 25(OH)D (25D; pre-metabolite). Changes in mRNA expression and protein expression after vitamin D exposure were analysed. Results indicate that while responses in normal and non-malignant breast tissues are similar between individuals, different tumour tissues are highly variable with regards to their gene expression and biological response. Collectively, malignant breast tissue responds well to active 1,25D, but not to the inactive pre-metabolite 25D. This may have consequences for the recommendation of vitamin D supplementation in breast cancer patients.