Neurotrophins (NTs) bind to two different classes of cell surface receptors, Trk receptor tyrosine kinases and p75NTR, both of which are expressed by neuroblastoma cells.
Expression of Trk receptors has been implicated in the pathogenesis and prognosis of embryonal tumors, including neuroblastoma, nephroblastoma, and medulloblastoma.
Collectively, these results indicate that EZH2 plays important roles in preventing the differentiation of NB cells and also that EZH2-related NTRK1 transcriptional regulation may be the key pathway for NB cell differentiation.
The aim of the present study was to investigate the effect of As<sub>2</sub>O<sub>3</sub> on Trk expression in NB cell lines and its potential therapeutic efficacy.
We suggest that the transcriptional program of neuroblastoma cells is modulated by Trk-receptor expression and basal activation rather than by ligand-induced activation.
In particular with the high-risk factors such as age of patient >1 year, MYCN amplification and low TRKA expression, the decreased expression of KLF4 was significantly associated with an unfavorable NB outcome.
Here, we used the SH-SY5Y human neuroblastoma cell line ectopically expressing either TrkA or TrkB as a model system to analyze the impact of Trk receptor expression on NHEJ-mediated DSB repair.
Consistent with this result, ZAR1-depleted NB cells showed well-differentiated phenotypes with elongated neurites and upregulated expression of TRKA and RET, which are markers for differentiated NB.
Expression level of trkA tyrosine kinase receptor for nerve growth factor is a major prognostic determinant of neuroblastoma, suggesting that defective trkA-mediated signaling is responsible for the tumorigenesis of this childhood malignancy.
Because another marker of poor prognosis in neuroblastoma tumors is high expression of brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor, TrkB, we sought to evaluate the involvement of BDNF and TrkB in the regulation of VEGF expression.
Exon-level expression analyses identify MYCN and NTRK1 as major determinants of alternative exon usage and robustly predict primary neuroblastoma outcome.
A total of 108 tumours were classified as neuroblastoma or ganglioneuroblastoma; 74 expressed TRKA protein, which strongly correlated with low stage, absence of N-MYC amplification, age (<1 year), CD44 expression and favourable clinical outcome.
A neuroblastoma is a common pediatric tumor derived from the neural crest, and the majority of favorable neuroblastomas express a high level of TRK-A mRNA.