Expression of 25 hydroxyvitamin D3-1alpha-hydroxylase in human endometrial tissue.
1,25(OH)(2)D(3) (calcitriol) has been shown to play an important role in cell proliferation, differentiation and immune responsiveness. The enzyme responsible for calcitriol synthesis 25 hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-OHase) has been reported in many human tissues. The aim of this study was to investigate the expression of 1alpha-OHase in gynaecological tissues. Using a highly specific nested touchdown PCR we examined the expression of 1alpha-OHase in normal and malignant endometrial tissue and in human endometrial Ishikawa cells. In addition, we analyzed the protein expression of 1alpha-OHase by Western blot. The expression of 1alpha-OHase in normal and malignant endometrial tissue and Ishikawa cells was detected and splice variants of the enzyme in Ishikawa cells were identified. These data suggest an alternative splicing of 1alpha-OHase in malignant endometrial tissue and cells. We postulate that the expression of 1alpha-OHase gene variants may contribute to the antiproliferative effects of calcitriol. In conclusion, the modulation of the 1alpha-OHase opens up a new target for vitamin D(3) related therapies in endometrial cancer.
Becker
Steffi
S
Department of Gynaecology and Obstetrics, University of Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany. steffi.becker2@gmx.de
Cordes
Tim
T
Diesing
Dagmar
D
Diedrich
Klaus
K
Friedrich
Michael
M
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D017398:Alternative Splicing / Q000235:genetics; D002460:Cell Line; D003001:Cloning, Molecular; D004717:Endometrium / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics
D012333:RNA, Messenger; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase