Insulin-like Growth Factor I: Action and Receptor Characterization in Human Prostate Cancer Cell Lines

Prostate. 1993;22(3):243-52. doi: 10.1002/pros.2990220307.

Abstract

The role of insulin-like growth factor I (IGF-I) in the growth and development of prostate cancer was studied using established human prostate cancer cell lines. Under steroid and growth factor-free culture conditions, IGF-I significantly stimulated the androgen-independent cell lines PC-3 and DU-145 to incorporate [3H]thymidine into DNA, while the androgen-dependent cell line, LNCaP, was not affected. However, in the presence of dihydrotestosterone (DHT), DNA synthesis of LNCaP cells was stimulated by IGF-I in a dose-dependent manner. None of the cell lines tested secreted an immunoreactive level of IGF-I into their conditioned medium. Characterization of receptors by ligand binding assays revealed that all prostate cancer cell lines tested express specific binding sites for IGF-I with similar dissociation constants (0.23-0.39 nM). Crosslinking studies supported the suggestion that 125I-IGF-I was bound to a receptor on these cells. The IGF-I receptor concentrations of androgen-independent cell lines were significantly higher than those of the androgen-dependent cell line. Androgen appeared to affect neither the expression of IGF-I receptors nor the secretion of IGF-I. The results suggest that IGF-I may play an important role in stimulating the growth and progression of prostate cancer.

MeSH terms

  • Binding, Competitive
  • Cell Division / physiology
  • Culture Media, Serum-Free
  • DNA, Neoplasm / biosynthesis
  • Dihydrotestosterone / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Epidermal Growth Factor / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor I / pharmacology*
  • Insulin-Like Growth Factor II / metabolism
  • Male
  • Neoplasms, Hormone-Dependent / metabolism*
  • Neoplasms, Hormone-Dependent / physiopathology
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / physiopathology
  • Receptor, IGF Type 1 / metabolism
  • Receptor, IGF Type 1 / physiology*
  • Tumor Cells, Cultured

Substances

  • Culture Media, Serum-Free
  • DNA, Neoplasm
  • Insulin
  • Dihydrotestosterone
  • Epidermal Growth Factor
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Receptor, IGF Type 1