Androgen receptor and vitamin D receptor in human ovarian cancer: Growth stimulation and inhibition by ligands

The data suggest that 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] and androg ens are essential for regulation of growth and differentiation in, e.g., hu man reproductive tissues. We investigated the possible cross-talk between 1 ,25(OH)(2)D-3 and androgens in the human ovarian cancer cell line OVCAR-3. Our data demonstrate that 1,25(OH)(2)D-3 and androgen (dihydrotestosterone, DHT) regulate the growth of OVCAR-3 cells. Nine days' treatment of OVCAR-3 cells with 100 nM DHT resulted in 48% stimulation of growth, whereas growt h inhibition (73%) was observed after treatment with 100 nM 1,25(OH)(2)D-3. The combination of 1,25(OH)(2)D-3 and DHT showed that 1,25(OH)(2)D-3 clear ly reduces the growth-stimulatory effect of DHT on OVCAR-3 cells. Moreover, Western blot analysis revealed that these cells contain receptors for 1,25 (OH)(2)D-3 (VDR) and androgen (AR). Expression of VDR and AR was up-regulat ed by their cognate ligands, Up-regulation of AR by 1,25(OH)(2)D-3 and of V DR by DHT provides evidence of cross-talk between 2 signaling pathways in O VCAR-3 cells, We also studied the immuno-histochemical distribution of VDRs and ARs in rat ovaries and human ovarian cancer cases. In rat ovaries, VDR s were observed mainly in granulosa and theca cells and ARs in granulosa ce lls and surface epithelium, In the human ovarian cancer cases studied, 43% were VDR-positive and 64% AR-positive, Combining the results suggests that the growth of ovarian tissue might be regulated by 1,25(OH)(2)D-3 and andro gen. Int. J. Cancer 86:40-46, 2000 (C) 2000 Wiley -Liss. Inc.