Background.
TrkA mRNA expression has been reported to be related to favorable outcome of neuroblastoma (NB). Previously, we found that interferon-␥ (IFN-␥) can enhance TrkA mRNA expression in NB cell lines. In the present study, we examined the effect of nerve growth factor (NGF) on IFN-␥-induced TrkA protein to clarify the relationship between TrkA and cell differentiation of NB. Procedure. The effect of IFN-␥ on the TrkA mRNA expression was screened in six human NB cell lines and a freshly prepared sample, SK-rib, from a stage IV patient. Using two of them, we examined their morphological change during simultaneous loading of NGF and IFN-␥. Tyrosine phosphorylation pattern after 5 min of NGF stimulation was also examined in immunoblot analysis with anti-gp140 trkA antibody and antiphospho tyrosine antibody. Results. After a 4-day treatment with 500 IU/ml IFN-␥, TrkA mRNA increased in five cell lines and SK-rib cells in association with growth inhibition. Although the degree of morphological differentiation did not increase in proportion to the TrkA expression induced by IFN-␥, continuous loading of both IFN-␥ and NGF caused marked morphological differentiation in a cultured KP-N-RT cell line and SK-rib cells during 10 days. Moreover, 5 min of NGF stimulation after IFN-␥ treatment caused the phosphorylation of TrkA protein and downstream proteins. Conclusions. IFN-␥ could induce the functional NGF receptor even in the aggressive phenotype of NB.