Regulation Of Insulin-Like Growth Factor (Igf) Ii And Igf Binding Protein 3 Autocrine Loop In Human Pc-3 Prostate Cancer Dells By Vitamin D Metabolite 1,25(Oh)(2)D-3 And Its Analog Eb1089

Prostate cancer and benign prostate hyperplasia (BPH) are major public health problems. Prostate epithelial cell proliferation is regulated by insulin-like growth factor I (IGF-I) which is mitogenic and anti-apoptotic, and IGF binding protein 3 (IGFBP-3) which is an apoptotic agent in these cells. We demonstrate that the 1,25(OH)(2)D-3 and its analog EB1089-induced growth inhibition was associated with increased IGFBP-3 mRNA abundance, IGFBP-3 mRNA stability, IGFBP-3 protein accumulation, and decreased IGF-II gene expression. Anti-IGF-II antibody and exogenous recombinant human IGFBP-3 inhibit PC-3 cell proliferation. The results document the inhibitory effects of 1,25(OH)(2)D-3 and EB 1089 on the IGF system of mitogens in prostate cancer cells, and suggest a potential therapeutic use of EB1089 in treatment of BPH and prostate cancer.