Interferon-gamma inhibits DNA synthesis and insulin-like growth factor-II expression in human neuroblastoma cells

J Neurosci Res. 1993 Apr 1;34(5):489-501. doi: 10.1002/jnr.490340502.

Abstract

Interferon-gamma (IFN-gamma) is known to be an antiproliferative, differentiating agent in many cell types, including neuroblastoma. In this study, we determined the effects of IFN-gamma on cellular growth and expression of insulin-like growth factor II (IGF-II) and IGF receptors in the human neuroblastoma cell line SH-SY5Y. Incubation of SH-SY5Y cells in IFN-gamma (20-100 U/ml) induced the formation of long neuritic processes. IFN-gamma treatment also induced decreases in [3H]TdR incorporation, as well as serum-dependent changes in cell number. Treatment with IFN-gamma reduced cell number 33% in the presence of serum but had no effect on cell number in the absence of serum. IGF-II mRNA content was 60% inhibited by IFN-gamma, and was not serum dependent. The concentration of immunoreactive IGF-II in SH-SY5Y conditioned medium was also reduced in the presence of IFN-gamma, to less than half of control levels. In contrast, type I IGF receptor mRNA content was increased more than three-fold after treatment with IFN-gamma and serum. Co-incubation in IFN-gamma (20-100 U/ml) and IGF-II (3-10 nM) prevented the inhibitory effects of IFN-gamma on [3H]TdR incorporation in serum-free media. Our results suggest that IFN-gamma may inhibit DNA synthesis and cell growth by interfering with an IGF-II/type I IGF receptor autocrine growth or survival mechanism.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Northern
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Division / drug effects
  • DNA, Neoplasm / biosynthesis*
  • Densitometry
  • Depression, Chemical
  • Humans
  • Insulin-Like Growth Factor II / biosynthesis*
  • Interferon-gamma / pharmacology*
  • Neurites / drug effects
  • Neuroblastoma / metabolism*
  • Neuroblastoma / pathology
  • RNA, Messenger / biosynthesis
  • Receptor, IGF Type 2 / biosynthesis
  • Tumor Cells, Cultured

Substances

  • DNA, Neoplasm
  • RNA, Messenger
  • Receptor, IGF Type 2
  • Insulin-Like Growth Factor II
  • Interferon-gamma