Differential effects of TrkA or TrkB expression on DNA repair capacity might contribute to the genomic stability of SY5Y neuroblastoma cells

The capacity to repair DNA double strand breaks (DSB) is crucial for genomic stability. The non-homologous end-joining pathway (NHEJ) for DNA repair is an important caretaker of the mammalian genome. High expression of TrkA is associated with favorable prognosis of neuroblastoma and a lack of structural chromosomal changes, whereas TrkB is expressed on aggressive neuroblastomas with high genomic instability. We here examined the contribution of TrkA or TrkB expression to the regulation of the NHEJ-pathway in neuroblastoma using SY5Y cells transfected with TrkA or TrkB. NHEJ activity was determined in cell-free extracts by a plasmid rejoining assay. Consistent with higher resistance to irradiation, SY5Y-TrkA extracts demonstrated a high rejoining activity in comparison to parental cells. In contrast, NHEJ activity was reduced in SY5Y-TrkB extracts. Microarray data obtained in the same model revealed up-regulation of XRCC4, a central effector gene of NHEJ, in SY5Y-TrkA cells. Expression data were confirmed by quantitative PCR and western blot. XRCC4 expression was also up-regulated in primary neuroblastomas with high TrkA expression. These data suggest a contribution of Trk receptors to the genomic stability in SY5Y neuroblastoma cells by mediating DSB-repair capacity. Further functional analyses of the NHEJ pathway may shed light on regulation of genomic stability in neuroblastoma and might partially explain current hypothetic models of neuroblastoma evolution.