Regulation of proliferation of prostate epithelial cells by 1,25-dihydroxyvitamin D-3 is accompanied by an increase in insulin-like growth factor binding protein-3

The biologically active form of vitamin D, 1,25-dihydroxyvitamin D-3 (1,25- (OH)A) has been shown to regulate the proliferation of human prostate epith elial cell lines. Since the insulin-like growth factor (IGF) system is invo lved in the transformation process of epithelial cells, the following study was undertaken to determine if the IGF system, in particular IGF binding p rotein-3 (IGFBP-3), is altered by 1,25-(OH)(2)D-3 in normal prostate epithe lial cells as part of a mechanism for inhibition of transformation. Two cel l systems were used in this study: (1) primary Cultures of benign human pro state epithelial cells (PECs) and (2) an SV40-T immortalized prostate epith elial cell Line (P153) that is non-tumorigenic. 1,25-(OH)(2)D-3 was added t o parallel sets of PECs and P153 cells in addition to the presence or absen ce of IGF-I or des(1-3)IGF-I. Treatment with 1,25-(OH)2D3 resulted in signi ficant growth inhibition of both PECs and P153 cells. Furthermore, 1,25-(OH )2D3 inhibited IGF-induced proliferation, but this was partially reversed b y high concentrations of IGF-I. Western ligand blots of condition media dem onstrated a significant increase in IGFBP-3; likewise Northern blots demons trated an increase in mRNA for IGFBP-3. Proliferation assays using an antib ody designed to block the IGF-independent effects of IGFBP-3 failed to reve rse the inhibitory effect of 1,25-(OH)(2)D-3. Thus, IGFBP-3 acts in an IGF- dependent manner to inhibit cell growth of benign prostate epithelial cells .