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)(2)D(3)) 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.


METHODS
We determined the expression of VDR, COX-2, 15-PGDH and the prostaglandin receptors EP(2)/EP(4) in normal and malignant breast tissue by real-time PCR and Western blot analysis, as well as 25(OH)(2)D(3) and PGE(2) plasma levels from healthy and breast cancer patients.


RESULTS
Significantly higher COX-2, lower VDR and lower EP(2) and EP(4) 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 winter time had significantly lower 25(OH)(2)D(3) and higher PGE(2) serum levels.


CONCLUSIONS
The inverse correlation between VDR and both COX-2 and 15-PGDH, as well as between PGE(2) and 25(OH)(2)D(3) levels, suggests a possible link between VDR-associated target genes and prostaglandin metabolism.
Thill
Marc
M
Department of Obstetrics and Gynecology, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany. marc.thill@uk-sh.de
Fischer
Dorothea
D
Hoellen
Friederike
F
Kelling
Katharina
K
Dittmer
Christine
C
Landt
Solveig
S
Salehin
Darius
D
Diedrich
Klaus
K
Friedrich
Michael
M
Becker
Steffi
S
D001943:Breast Neoplasms / Q000378:metabolism*; D002117:Calcitriol / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D011453:Prostaglandins / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
D011453:Prostaglandins; D018167:Receptors, Calcitriol; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D002117:Calcitriol; D015232:Dinoprostone