Receptors for 1,25-dihydroxyvitamin D3 in gynecologic neoplasms.
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.
Saunders
D E
DE
C. S. Mott Center for Human Growth & Development, Wayne State University, Detroit, Michigan 48201.
Christensen
C
C
Lawrence
W D
WD
Malviya
V K
VK
Malone
J M
JM
Williams
J R
JR
Deppe
G
G
D002117:Calcitriol / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000648:ultrastructure*; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000032:analysis / Q000378:metabolism*; D012509:Sarcoma / Q000378:metabolism / Q000648:ultrastructure*; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000648:ultrastructure*
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002117:Calcitriol