Vitamin D Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin D, including details on sources, melanin, benefits, deficiency, supplements, calcium absorption.

Autocrine metabolism of vitamin D in normal and malignant breast tissue.

Townsend K, Banwell CM, Guy M, Colston KW, Mansi JL, Stewart PM, Campbell MJ, Hewison M

Division of Medical Sciences, Institute of Biomedical Research, Endocrinology and Metabolism, University of Birmingham, Birmingham, United Kingdom.

PURPOSE: Vitamin D seems to exert a protective effect against common cancers, although this does not correlate with circulating levels of active 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], indicating a more localized activation of vitamin D. The aim of this study was to investigate the significance of this in breast cancer. EXPERIMENTAL DESIGN: Quantitative reverse transcription-PCR analysis of mRNA expression was carried out for the vitamin D-activating enzyme 1alpha-hydroxylase, the catabolic enzyme 24-hydroxylase, and the vitamin D receptor in 41 tumors and paired nonneoplastic tissue as well as breast cancer cell lines. Immunohistochemistry was used to assess 1alpha-hydroxylase protein expression, and enzyme assays were used to quantify vitamin D metabolism. RESULTS: Expression of mRNA for 1alpha-hydroxylase (27-fold; P < 5 x 10(-11)), vitamin D receptor (7-fold; P < 1.5 x 10(-8)), and 24-hydroxylase (4-fold; P < 0.02) was higher in breast tumors. 1alpha-Hydroxylase enzyme activity was also higher in tumors (44.3 +/- 11.4 versus 12.4 +/- 4.8 fmol/h/mg protein in nonneoplastic tissue; P < 0.05). However, production of inactive 1,24,25-trihydroxyvitamin D3 was also significantly higher in tumors (84.8 +/- 11.7 versus 33.6 +/- 8.5 fmol/h/mg protein; P < 0.01). Antisense inhibition of 24-hydroxylase in vitro increased antiproliferative responses to 1,25(OH)2D3. CONCLUSION: These data indicate that the vitamin D-activating enzyme 1alpha-hydroxylase is up-regulated in breast tumors. However, dysregulated expression of 24-hydroxylase seems to abrogate the effects of local 1,25(OH)2D3 production in tumors by catalyzing catabolism to less active vitamin D metabolites. The enzymes involved in autocrine metabolism of vitamin D in breast tissue may therefore provide important targets for both the prevention and treatment of breast cancer.

Published 3 May 2005 in Clin Cancer Res, 11(9): 3579-86.
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