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

Interferon-γ (IFN-γ) is known to be an antiproliferative, differentiation agent in many cell types, including neuroblastoma. In this study, we determined the effects of IFN-γ 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-γ (20–100 U/ml) induced the formation of long neuritic processes. IFN-γ treatment also induced decreases in [³H]TdR incorporation, as well as serum-dependent changes in cell number. Treatment with IFN-γ 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-γ, and was not serum dependent. The concentration of immunoreactive IGF-II in SH-SY5Y conditioned medium was also reduced in the presence of IFN-γ, 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-γ and serum. Co-incubation in IFN-γ (20–100 U/ml) and IGF-II on (3–10 nM) prevented the inhibitory effects of IFN-γ on [³H]TdR ncorporation in serum-free media. Our results suggest that IFN-γ may inhibit DNA synthesis and cell growth by interfering with an IGF-II/type I IGF receptor autocrine growth or survival mechanism.