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

Abstract

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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See also:

- Vitamin D (analogues and/or derivatives) and cancer;

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