Regulation of insulin-like growth factor (IGF) II and IGF binding protein 3 autocrine loop in human PC-3 prostate cancer cells by vitamin D metabolite 1,25(OH)2D3 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)2D3 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)2D3 and EB1089 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.
Huynh
H
H
Lady Davis Research Institute of the Jewish General Hospital and Departments of Medicine, McGill University, Montreal, Quebec H3T 1E2, Canada.
Pollak
M
M
Zhang
J C
JC
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D002117:Calcitriol; C078903:seocalcitol