Insulin-like growth factor binding protein-3 is regulated by dihydrotestosterone and stimulates deoxyribonucleic acid synthesis and cell proliferation in LNCaP prostate carcinoma cells

Endocrinology. 2000 Jul;141(7):2401-9. doi: 10.1210/endo.141.7.7534.


We have investigated the production and actions of a growth regulatory protein, insulin-like growth factor binding protein (IGFBP)-3, in the androgen-responsive prostate carcinoma cell line LNCaP. Confluent monolayers of cells secreted approximately 0.7 ng/ml IGFBP-3 over 24 h. Dihydrotestosterone (DHT, 10 nM) and 1,25-dihydroxyvitamin D3 (vitamin D, 10 nM) increased IGFBP-3 in media to 149 +/- 15% and 206 +/- 18% of control, respectively, when added separately, and to 453 +/- 28% of control when used in combination. IGFBP-2, secreted at approximately 25-fold higher concentrations than IGFBP-3, was increased 50% by 10 nM DHT, but there was no effect of vitamin D on IGFBP-2 production in the absence or presence of DHT. Cell-associated IGFBP-3, and immunoreactive IGFBP-3 species of 20 kDa and 30 kDa were also increased in response to vitamin D plus DHT. A combination of vitamin D and DHT increased DNA synthesis in LNCaP cells 3-fold, and this was at least partly mediated by endogenous IGFBP-3 because anti-IGFBP-3 IgG, but not nonimmune serum IgG, reduced the stimulatory effect of vitamin D and DHT from 293 +/- 11.6% to 161 +/- 30.7% of control levels (P < 0.0001). Basal and DHT plus vitamin D-stimulated thymidine incorporation was significantly increased by 50 ng/ml human plasma-derived purified IGFBP-3. After 4 days treatment with vitamin D plus DHT, or pure IGFBP-3, LNCaP cell numbers were increased relative to control. These results indicate a role for IGFBP-3 in the proliferation of androgen-responsive prostate carcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Division / physiology
  • DNA / biosynthesis*
  • DNA, Neoplasm / biosynthesis
  • Dihydrotestosterone / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Humans
  • Insulin-Like Growth Factor Binding Protein 2 / metabolism
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Insulin-Like Growth Factor Binding Protein 3 / pharmacology
  • Insulin-Like Growth Factor Binding Protein 3 / physiology*
  • Insulin-Like Growth Factor I / pharmacology
  • Male
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*
  • Thymidine / metabolism
  • Tumor Cells, Cultured
  • Vitamin D / pharmacology


  • DNA, Neoplasm
  • Drug Combinations
  • Insulin-Like Growth Factor Binding Protein 2
  • Insulin-Like Growth Factor Binding Protein 3
  • Dihydrotestosterone
  • Vitamin D
  • Insulin-Like Growth Factor I
  • DNA
  • Thymidine