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

Anticancer Res. 2010 May;30(5):1673-9.

Abstract

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.

Materials and 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.

Conclusion: 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.

MeSH terms

  • Breast Neoplasms / metabolism*
  • Calcitriol / metabolism*
  • Carcinoma / metabolism
  • Dinoprostone / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hydroxyprostaglandin Dehydrogenases / metabolism
  • Middle Aged
  • Prognosis
  • Prostaglandins / metabolism*
  • Receptors, Calcitriol / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tissue Distribution

Substances

  • Prostaglandins
  • Receptors, Calcitriol
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase
  • Calcitriol
  • Dinoprostone