Prostaglandin metabolising enzymes and PGE₂ are inversely correlated with vitamin D receptor and 25(OH)₂D₃ in breast cancer

Background: Breast cancer is associated with inflammatory processes based on an up-regulation of cyclooxygenase-2 (COX-2) expression. The antiproliferative effects of calcitriol (1,25(OH)₂D₃) mediated via the vitamin D receptor (VDR) render vitamin D a promising target in breast cancer therapy. First data suggest a correlation between vitamin D and prostaglandin metabolism. Materials and Methods: We determined the expression of VDR, COX-2, 15-PGDH and the prostaglandin receptors EP₂/EP ₄ in normal and malignant breast tissue by real-time PCR and Western blot analysis, as well as 25(OH)₂D₃ and PGE₂ plasma levels from healthy and breast cancer patients. Results: Significantly higher COX-2, lower VDR and lower EP₂ and EP₄ receptor protein levels in the malignant tissue and a significantly lower 15-PGDH protein level in normal breast tissue were detected. Breast cancer patients older than 45 years, diagnosed and sampled in the wintertime had significantly lower 25(OH)₂D₃ and higher PGE₂ serum levels. Conclusion: The inverse correlation between VDR and both COX-2 and 15-PGDH, as well as between PGE₂ and 25(OH)₂D₃ levels, suggests a possible link between VDR-associated target genes and prostaglandin metabolism.