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)2D3) 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 E2 (PGE2) synthesizing enzyme. The PGE2 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)2D3 on the expression of COX-2 and 15-PGDH.


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.


CONCLUSIONS
A possible link between VDR-associated target genes and prostaglandin metabolism is suggested.
Thill
Marc
M
Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, Germany. marc.thill@uk-sh.de
Fischer
Dorothea
D
Becker
Steffi
S
Cordes
Tim
T
Dittmer
Christine
C
Diedrich
Klaus
K
Salehin
Darius
D
Friedrich
Michael
M
D001940:Breast / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D011453:Prostaglandins; D018167:Receptors, Calcitriol; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D051546:Cyclooxygenase 2