Vitamin D is an essential molecule obtained either by UV irradiation of the skin, or ingested through diet or supplementation. Sequential hydroxylations of vitamin D are required to generate the inactive precursor 25-hydroxyvitamin D (25D), and the active metabolite 1,25-dihydroxyvitamin D (1,25D) which activates the vitamin D receptor to alter transcription of target genes. In addition to its role in calcium homeostasis, vitamin D has been shown to have anti-proliferative, apoptotic and immunomodulating effects. Furthermore, many epidemiological studies have shown a link between a low vitamin D status and an increased risk of breast cancer. However, the mechanistic basis of this link remains unknown. We have utilized a breast explant system whereby fresh tumour and matched non-malignant breast tissues are obtained from women undergoing mastectomies. These tissues are placed on gelatin sponges in tissue culture media supplemented with either 25D or 1,25D. Tissues are then collected and analysed for alterations in gene expression and biological response. This system allows for the analysis of dynamic changes in viable tissue in response to exogenously applied compounds, and can easily be used to examine other compounds of interest. Explanted non-malignant and tumour tissue both displayed an increase in expression of the vitamin D metabolizing enzyme CYP24A1 when directly treated with 1,25D. In response to the precursor molecule 25D, non-malignant breast tissue showed a similar pattern of enzyme induction, indicating an intact and competent vitamin D metabolic pathway in these tissues. Metabolism in breast tumour tissue however was somewhat disrupted, with some cases showing little potential in converting 25D to the active metabolite 1,25D. Proliferation markers have also been examined in the non-malignant and tumour breast samples. Interestingly, some tumour specimens did not show any change in proliferation despite favourable changes in gene expression, indicating further dysregulation of vitamin D metabolism in these samples. These data will have implications for any future clinical studies of vitamin D supplementation to complement current chemopreventative therapies.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5159. doi:1538-7445.AM2012-5159