Prostaglandin Metabolizing Enzymes in Correlation with Vitamin D Receptor in Benign and Malignant Breast Cell Lines

Background: The antiproliferative effects of calcitriol (1,25(OH)(2)D-3) mediated via the vitamin D receptor (VDR), render the biologically active form of vitamin D a promising target in breast cancer therapy. Furthermore, breast cancer is associated with inflammatory processes based on an up-regulation of cyclooxygenase-2 (COX-2) expression, the prostaglandin E-2 (PGE(2)) synthesizing enzyme. The PGE(2) metabolizing enzyme, 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is described as a tumor suppressor in cancer. First references suggest a correlation between vitamin D and prostaglandin metabolism through the impact of 1,25(OH)(2)D-3 on the expression of COX-2 and 15-PGDH. Materials and Methods: The expression of VDR, COX-2 and 15-PGDH in benign MCF-10F and malignant MCF-7 breast cells was determined by real-time PCR (RT-PCR) and Western blot analysis. Results: Although the RT-PCR data were divergent from those obtained from the Western blot analysis, the COX-2 protein expression was MCF-7 2-fold higher in the MCF-7 compared to the MCF-10F cells. Moreover, a correlation of 15-PGDH to VDR by RT-PCR was found in both cell lines. The VDR protein levels were inversely correlated to the 15-PGDH protein levels and revealed that the MCF-10F cells had the highest VDR expression. Conclusion: A possible link between VDR-associated target genes and prostaglandin metabolism is suggested.