Prostaglandin metabolizing enzymes in correlation with vitamin D receptor in benign and malignant breast cell lines

Anticancer Res. 2009 Sep;29(9):3619-25.

Abstract

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.

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.

MeSH terms

  • Breast / cytology
  • Breast / enzymology
  • Breast / metabolism*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cyclooxygenase 2 / metabolism
  • Humans
  • Hydroxyprostaglandin Dehydrogenases / metabolism
  • Prostaglandins / metabolism*
  • Receptors, Calcitriol / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Prostaglandins
  • Receptors, Calcitriol
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase
  • Cyclooxygenase 2