25-Hydroxyvitamin D-1alpha-hydroxylase (lalpha-OHase) is expressed in prostate cells. The expression suggests that local production of 1,25-dihydroxyvitamin D could provide an important cell growth regulatory mechanism. However, there is differential expression of @entity3867 activity among the primary cultures of prostate cells derived from cancerous, @entity1067 and normal tissue, and among noncancerous (PZHPV-7) and various @entity5 cell lines ( @entity10642 , DU145). No activity was found in @entity5 cell line LNCaP. The observed marked decrease in @entity3867 activity in @entity263 cells suggests some defect of the @entity3867 in these cells. Using luciferase reporter gene assay, we observed a step-wise decrease in the basal promoter activity in two truncated promoter fragments, @entity6484 (-1,100 bp) and AN5 (-394 bp), with the highest basal activities found in PZHPV-7 and with loss of promoter activity in LNCaP. In order to understand the mechanism underlying the differential promoter activities among different prostate cells, we investigated the possible role of phosphorylation of @entity10366 ( @entity10366 ) on the regulation of @entity3867 promoter activity in the four prostate cell lines. First we compared the levels of @entity10366 phosphorylation among PZHPV-7, DU145, @entity10642 and LNCaP cells by Western blot analysis using antibody against phosphorylated @entity10366 . We observed that @entity10366 was phosphorylated to a greater extent in PZHPV-7 than in DU145 cells. No significant phosphorylation of @entity10366 was found in @entity10642 and LNCaP cells. Next, we utilized activators and inhibitors of protein kinase A (PKA), @entity7131 ( @entity7131 ), mitogen-activated protein kinase kinase (MAPKK) and calcium/calmodulin-dependent protein kinase II (CaMKII) to determine which kinases might be involved in phosphorylating the @entity10366 in PZHPV-7 cells. We demonstrated that forskolin (an activator of PKA) increased the @entity6484 basal promoter activity 50%, whereas H-89 (an inhibitor of PKA) inhibited the basal and forskolin-stimulated @entity6484 promoter activity 40% and 70%, respectively. We also showed that PD98059 (an inhibitor of MAPKK) decreased the @entity6484 promoter activity 70%. Phorbol 12-myristate 13-acetate (an activator of @entity7131 ), GF109203 (an inhibitor of @entity7131 ) and KN-93 (an inhibitor of CaMKII) had no effect on @entity6484 promoter activity in PZHPV-7 cells. Thus, our results suggest that differential phosphorylation of @entity10366 through PKA and MAPK pathways may be involved in the regulation of @entity3867 promoter activity.

Vitamin D autocrine system and XXXX .

@entity10642 :: ('3853', 'Gene') :: ['PC-3'] @entity263 :: ('MESH:D011471', 'Disease') :: ['prostate cancer'] @entity3867 :: ('1594', 'Gene') :: ['1alpha-OHase'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancer'] @entity1067 :: ('MESH:D011470', 'Disease') :: ['benign prostatic hypertrophy'] @entity7131 :: ('MESH:D020151', 'Disease') :: ['protein kinase C', 'PKC'] @entity10366 :: ('1385', 'Gene') :: ['cyclic AMP response element binding protein', 'CREB'] @entity6484 :: ('5080', 'Gene') :: ['AN2']
@entity263 :: (MESH:D011471,Disease) :: ['prostate cancer']
