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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal
  • Antineoplastic Agents / pharmacology*
  • Calcitriol / analogs & derivatives*
  • Calcitriol / pharmacology*
  • Cell Division / drug effects
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism*
  • Insulin-Like Growth Factor II / metabolism*
  • Male
  • Prostatic Neoplasms / metabolism*
  • RNA, Messenger / metabolism
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Insulin-Like Growth Factor Binding Protein 3
  • RNA, Messenger
  • Insulin-Like Growth Factor II
  • Calcitriol
  • seocalcitol