Abstract
The LNCaP prostatic carcinoma cell line was examined for the presence of specific receptors for 1α,25-dihydroxyvitamin D3 [1α,25-(OH)2D3]. Whole cell binding studies identified approximately 2500 high-affinity (Kd = 1.4 × 10−9) binding sites per cell. Competition studies revealed that these receptors are specific for the 1α,25(OH)2 metabolite. Binding studies using the synthetic androgen R1881 indicate that separate androgen and vitamin D3 receptors exist in LNCaP cells. The vitamin D3 receptors sediment at approximately 3.5S on linear sucrose gradients. The sedimentation coefficient could be shifted with a monoclonal anti-vitamin D3 receptor antibody (9A7γ) but not with a monoclonal antibody to the androgen receptor (AN1-15). The receptor/ligand complex elutes from native DNA cellulose at 0.2 m KCl. Northern blot analysis identified an mRNA of approximately 4.6 kilobases which hydridized with a specific vitamin D3 receptor complementary DNA probe (hVDR). In the absence of androgens, 1α,25(OH)2D3 stimulated growth and prostate-specific antigen production by LNCaP cells in a dose-dependent fashion. Dose-response curves indicated that at physiological concentrations (10−9 m) 1α,25(OH)2D3 was mitogenic, whereas at higher concentrations (10−8 m) it promotes differentiation. These studies suggest that 1α,25(OH)2D3 could play an important role in the natural history of and response to hormone therapy by prostatic cancer.
Footnotes
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↵1 This work was supported in part by a grant from the Cancer League of Colorado (G. J. M.).
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↵2 To whom requests for reprints should be addressed, at Department of Pathology (B216), University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262.
- Received September 10, 1991.
- Accepted November 14, 1991.
- ©1992 American Association for Cancer Research.
Volume 52, Issue 3
