Neuronal differentiation in human neuroblastoma cells by nerve growth factor following TrkA up-regulation by interferon-?

Abstract

Background TrkA mRNA expression has been reported to be related to favorable outcome of neuroblastoma (NB). Previously, we found that interferon‐γ (IFN‐γ) can enhance TrkA mRNA expression in NB cell lines. In the present study, we examined the effect of nerve growth factor (NGF) on IFN‐γ‐induced TrkA protein to clarify the relationship between TrkA and cell differentiation of NB. Procedure The effect of IFN‐γ 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‐γ. Tyrosine phosphorylation pattern after 5 min of NGF stimulation was also examined in immunoblot analysis with anti‐gp140trkA antibody and antiphospho tyrosine antibody. Results After a 4‐day treatment with 500 IU/ml IFN‐γ, 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‐γ, continuous loading of both IFN‐γ 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‐γ treatment caused the phosphorylation of TrkA protein and downstream proteins. Conclusions IFN‐γ could induce the functional NGF receptor even in the aggressive phenotype of NB. Med. Pediatr. Oncol. 34:394–401, 2000. © 2000 Wiley‐Liss, Inc.

Differential expression of delta-like gene and protein in neuroblastoma, ganglioneuroblastoma and ganglioneuroma

“…The cause of trans-differentiation of one form into another is unknown, but probably involves pathways that signal the cell to differentiate. 1 Delta-like protein (dlk) is a member of the epidermal growth factor (EGF)-like family, which includes proteins such as Notch, Delta, and Serrate in the control of cell differentiation. 2 Structural analysis reveals that dlk contains six EGF-like repeats in the extracellular domains, and a short intracellular domain.…”

Nerve Growth Factor Expression and Its Receptors TrkA and p75NTR in Peri-Implantitis Lesions

“…20 Certain hormones (eg, oestrogen), inflammatory cytokines (eg, interferon-gamma), and NGF itself increase TrkA expression in different cell types. [36][37][38][39] All these data suggest that inflammatory signals upregulate or activate both NGF and TrkA expressions. 11 Moreover, some studies have demonstrated that NGF is capable of autocrine or paracrine activation of inflammatory cells.…”

NGF and its receptors TrkA and p75NTR in the epithelium of oral lichen

“…oestrogen), inflammatory cytokines (e.g. interferon‐gamma) and NGF itself can increase TrkA expression in different cell types (29–32). Changes in TrkA expression in skin diseases have been reported before but the results are not consistent (18, 20, 21).…”