Abstract

1,25(OH)2D3 (calcitriol) has been shown to play an important role in cell proliferation, differentiation and immune responsiveness. The enzyme responsible for calcitriol synthesis 25 hydroxyvitamin D3-1α-hydroxylase (1α-OHase) has been reported in many human tissues. The aim of this study was to investigate the expression of 1α-OHase in gynaecological tissues. Using a highly specific nested touchdown PCR we examined the expression of 1α-OHase in normal and malignant endometrial tissue and in human endometrial Ishikawa cells. In addition, we analyzed the protein expression of 1α-OHase by Western blot. The expression of 1α-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 1α-OHase in malignant endometrial tissue and cells. We postulate that the expression of 1α-OHase gene variants may contribute to the antiproliferative effects of calcitriol. In conclusion, the modulation of the 1α-OHase opens up a new target for vitamin D3 related therapies in endometrial cancer.

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