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-alpha (RXRalpha) 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 RXRalpha 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 in choriocarcinoma cells. Differentiation of BeWo cells 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.
Pospechova
Katerina
K
Department of Biological and Medical Science, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Heyrovsky, Hradec Kralove, Czech Republic.
Rozehnal
Veronika
V
Stejskalova
Lucie
L
Vrzal
Radim
R
Pospisilova
Nada
N
Jamborova
Gabriela
G
May
Karen
K
Siegmund
Werner
W
Dvorak
Zdenek
Z
Nachtigal
Petr
P
Semecky
Vladimir
V
Pavek
Petr
P
D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002469:Cell Separation; D002822:Choriocarcinoma / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D017930:Genes, Reporter; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D047490:Retinoid X Receptor alpha / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D015820:Cadherins; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D047490:Retinoid X Receptor alpha; D004958:Estradiol; D008156:Luciferases; D002117:Calcitriol