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

View file »
Link:
http://hdl.handle.net/2027.42/50226
Collection:
Creators:
Feldman, Eva L. Martin, Donna M. Carlson, Robert O.
Contributors:
Department of Neurology and the Neuroscience Program, The University of Michigan, Ann Arbor, Michigan Department of Biochemistry, The University of Michigan, Ann Arbor, Michigan Department of Neurology and the Neuroscience Program, The University of Michigan, Ann Arbor, Michigan 1120C Neuroscience Laboratory, 1103 E. Huron Ave., Ann Arbor, MI 48104
Description
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 [ 3 H]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 [ 3 H]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. 
Rights
IndexNoFollow 
Publisher
Wiley Subscription Services, Inc., A Wiley Company 
Access:
Instructions in case access is denied