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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.

作者信息

Huynh H, Pollak M, Zhang J C

机构信息

Lady Davis Research Institute of the Jewish General Hospital and Departments of Medicine, McGill University, Montreal, Quebec H3T 1E2, Canada.

出版信息

Int J Oncol. 1998 Jul;13(1):137-43. doi: 10.3892/ijo.13.1.137.

DOI:10.3892/ijo.13.1.137
PMID:9625815
Abstract

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.

摘要

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