Vitamin D--metabolism in the human breast cancer cell line MCF-7

Anticancer Res. 2006 Jul-Aug;26(4A):2755-9.

Abstract

Background: The three main vitamin D metabolizing enzymes, vitamin D3-25-hydroxylase (25-OHase, 25-hydroxylase), 25-hydroxyvitamin D3-1alpha-hydroxylase (1alpha-OHase, 1alpha-hydroxylase) and 25-hydroxyvitamin D3-24-hydroxylase (24-OHase, 24-hydroxylase), have been described in malignant breast tissue. This in vitro study aimed to obtain more information regarding the regulation of these enzymes in the human breast cancer cell line MCF-7.

Materials and methods: Vitamin D receptor (VDR)- positive MCF-7 cells in culture were stimulated with the vitamin D metabolites vitamin D3, 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 for 24, 48; 72 and 96 hours in physiological and supraphysiological concentrations. The expressions of 25-hydroxylase, 1alpha-hydroxylase and 24-hydroxylase and their changes after stimulation were assessed by real-time PCR.

Results: The expression of 25-hydroxylase was slightly influenced by vitamin D3. The expression of 1alpha-hydroxylase was induced after stimulation with vitamin D3 and 25-hydroxyvitamin D3. Stimulation with 1,25-dihydroxyvitamin D3 markedly increased the expression of 24-hydroxylase time- and dose-dependently.

Conclusion: Our results demonstrated that MCF-7 cells are able to regulate the expression of 24-hydroxylase. This might be a mechanism for these tumor cells to protect themselves against the antiproliferative and apoptosis-inducing effects of calcitriol.

MeSH terms

  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism*
  • Calcifediol / metabolism
  • Calcifediol / pharmacology
  • Calcitriol / analogs & derivatives
  • Calcitriol / metabolism
  • Calcitriol / pharmacology
  • Cell Line, Tumor
  • Cholestanetriol 26-Monooxygenase
  • Humans
  • Steroid Hydroxylases / metabolism
  • Vitamin D / metabolism*
  • Vitamin D3 24-Hydroxylase

Substances

  • 1,25-dihydroxy-19-norvitamin D3
  • Vitamin D
  • Steroid Hydroxylases
  • CYP27A1 protein, human
  • Cholestanetriol 26-Monooxygenase
  • Vitamin D3 24-Hydroxylase
  • Calcitriol
  • Calcifediol