Metabolism of vitamin D in the human choriocarcinoma cell line JEG-3.
Calcitriol is an antiproliferative prodifferentiating secosteroid that exerts a protective role for some kinds of cancer. Alterations in 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1) activity have been found in some tumor cells, but there are no studies performed in human choriocarcinoma. In the present work, calcitriol production and CYP27B1 gene regulation were studied in the human choriocarcinoma cell line JEG-3, and compared with normal human syncytiotrophoblasts (hS) in culture. In JEG-3 cells, secretion of [(3)H]calcitriol was significantly less (P<0.001) than in hS (45+/-17fmol/mg protein versus 174+/-87fmol/mg protein, respectively; n=8). CYP27B1 mRNA was similar in both JEG-3 and hS cells; but the protein was detected only in hS extracts. In contrast to the hS, JEG-3 CYP27B1 gene expression was not regulated by calcitriol or by a cAMP analogue. Our results indicate that in JEG-3 cells calcitriol production is diminished due to CYP27B1 dysregulation and low protein content, and suggest that hyperproliferation could be a consequence of these alterations.
Avila
Euclides
E
Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Tlalpan 14000, Mexico, D.F., Mexico.
Díaz
Lorenza
L
Barrera
David
D
Arranz
Celeste
C
Halhali
Ali
A
Larrea
Fernando
F
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D045744:Cell Line, Tumor; D048430:Cell Shape; D002822:Choriocarcinoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D014327:Trophoblasts / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism*
D014807:Vitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase