Endocrinology, Vol 137, 1554-1561, Copyright © 1996 by Endocrine Society

ARTICLES

Stable expression of the nuclear vitamin D receptor in the human prostatic carcinoma cell line JCA-1: evidence that the antiproliferative effects of 1 alpha, 25-dihydroxyvitamin D3 are mediated exclusively through the genomic signaling pathway

TE Hedlund, KA Moffatt and GJ Miller
Department of Pathology, University of Colorado Health Sciences Center, Denver 80262, USA.

The secosteroid hormone 1 alpha, 25-dihydroxyvitamin D3 [1,25-(OH)2D3] has been found to regulate the growth and differentiation of human prostate cancer cells, although the precise mechanisms mediating these effects have not been defined. 1,25-(OH)2D3 is capable of acting through both nongenomic signaling pathways involving a membrane- associated receptor and genomic pathways involving the nuclear vitamin D receptor (VDR). The primary purpose of this study was to directly evaluate the role of the nuclear VDR in mediating the growth inhibitory effects of 1,25-(OH)2D3 on human prostate cancer cells. The cell line JCA-1 was used because it fails to express detectable number of VDRs and is not measurable affected by 1,25-(OH)2D3 in growth studies. These cells were stably transfected with a wild-type VDR complementary DNA construct producing the following results: 1) the expression of high affinity nuclear VDRs, 2) the dose-dependent inhibition of growth by 1,25-(OH)2D3, and 3) a significant increase in 24-hydroxylase up- regulation by 1,25-(OH)2D3 compared to that in controls. These data indicate that nuclear VDR expression is sufficient to mediate the antiproliferative effects of 1,25-(OH)2D3 on prostate cancer cells. In addition, because the stereoisomer 1 beta, 25-dihydroxyvitamin D3 failed to block these antiproliferative effects, we conclude that nongenomic mechanisms of action are not requisite for growth inhibition by 1,25-(OH)2D3.

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