Expression und Funktion des Vitamin-D-Rezeptors in malignen Keimzelltumoren des Hodens

Testicular germ cell tumours (TGCT) are the most common malignancy in young men. They are clinical and histological subdivided in seminomas and non-seminomas. 1,25-dihydroxyvitamin D3 (1;25(OH)2D3) is the active form of Vitamin D and exerts its actions via a specific intracellular vitamin D receptor (VDR). Several investigations showed, in addition to the physiological occurrence of the VDR in various tissues, a VDR expression in different human malignancies in the recent years. Further 1;25(OH)2D3 plays an important role in the regulation of cell proliferation and differentiation. In different normal and malignant cell types antiproliferative and pro-differentiating effects of 1;25(OH)2D3 are described. We investigated the expression and function of VDR in TGCT. In immunohistochemistry, quantitative RT PCR and western blot analyses we demonstrated for the first time, that primary TGCT as well as TGCT cell lines express VDR-RNA and VDR-Protein. Furthermore TGCT cell lines ! show a decrease of proliferation after Vitamin D stimulation. Furthermore we investigated the Vitamin D regulated genes VDR, NCOR1, NCOR2, TRIP15, GADD45, MAPKAPK2, CYP24A1 and CYP27B1 after Vitamin D stimulation.