Expression and activity of vitamin D receptor in the human placenta and in choriocarcinoma BeWo and JEG-3 cell lines

Vitamin D receptor (VDR) regulates the expression of many genes involved in mineral metabolism, cellular proliferation, differentiation and drug biotransformation. We studied the expression and activity of VDR and its heterodimerization partner retinoid X receptor-a (RXR alpha) in choriocarcinoma trophoblast cell lines BeWo and JEG-3, in comparison with human isolated placental cytotrophoblasts and human full term placenta. We found that VDR and RXR alpha are localised in the human term placenta trophoblast and expressed in isolated cytotrophoblasts. However, we found low expression and no transcriptional activity of VDR in used choriocarcinoma cell lines. The inhibitor of DNA methylation, 5-deoxy-3'-azacytidine, and histone deacetylase inhibitor sodium butyrate partially restored the expression of VDR, suggesting an epigenetic suppression of the gene inchoriocarcinoma cells. Differentiation of BeWocells resulted in up-regulation of VDR mRNA. Finally, we observed a non-genomic effect of 1,25(OH)(2)D-3 in the activation of the extracellular signal-regulated kinase (ERK) signalling pathway in JEG-3 cells. In conclusion, our results suggest an epigenetic repression of VDR gene expression and activity in choriocarcinoma cell lines, and a non-genomic effect of 1,25(OH)(2)D-3 in JEG-3 cells. (c) 2008 Elsevier Ireland Ltd. All rights reserved.