Receptors for 1,25-dihydroxyvitamin D3 in gynecologic neoplasms

Gynecol Oncol. 1992 Feb;44(2):131-6. doi: 10.1016/0090-8258(92)90028-h.

Abstract

To determine if gynecologic malignancies are candidates for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) therapy we measured vitamin D receptor (VDR) levels in 11 tumor specimens using a radiolabeled ligand-binding assay. VDR was demonstrated in 3 of 6 ovarian tumors and 1 of 1 uterine sarcomas, but not in endometrial tumors (2), cervical tumors (1), or Krukenberg tumors (1). Scatchard plots revealed that [3H]1,25(OH)2D3 was bound to a single class of high-affinity (Kd = 0.3 to 0.6 nM), saturable sites characteristic of authentic 1,25(OH)2D3 receptors. Specificity of binding activity for 1,25(OH)2D3, the active vitamin D3 metabolite, was demonstrated by failure of 25-hydroxy- and 24,25-dihydroxyvitamin D3 to compete effectively against 1,25(OH)2D3 binding in total cellular tumor extracts. The ovarian carcinoma cell line NIH:OVCAR3 was shown to possess VDR (binding capacity = 137 fmol/mg protein, Kd = 0.48 nM). A 3-day incubation of NIH:OVCAR3 cells with 100 nM 1,25(OH)2D3 resulted in 49% inhibition of cell growth. The growth inhibition of an ovarian carcinoma line and the observation that 36% of gynecologic tumors assayed were shown to be VDR-positive suggest that further study is warranted to delineate the mechanism and possible therapeutic aspects of 1,25(OH)2D3 action in gynecologic tumors.

MeSH terms

  • Calcitriol / metabolism
  • Calcitriol / therapeutic use
  • Female
  • Humans
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / ultrastructure*
  • Receptors, Calcitriol
  • Receptors, Steroid / analysis
  • Receptors, Steroid / metabolism*
  • Sarcoma / metabolism
  • Sarcoma / ultrastructure*
  • Uterine Neoplasms / drug therapy
  • Uterine Neoplasms / metabolism
  • Uterine Neoplasms / ultrastructure*

Substances

  • Receptors, Calcitriol
  • Receptors, Steroid
  • Calcitriol