The role of EGFR trafficking in neuroblastoma

20003 Background: Signaling through growth factor receptors is important in neuroblastoma pathogenesis. Chromosome 1p36 is commonly deleted in neuroblastoma tumors and is associated with a poor prognosis. UBE4B, a gene in 1p36, has been reported mutated in high- risk neuroblastoma. We have found a direct interaction between UBE4B and hrs, a protein required for epidermal growth factor receptor (EGFR) trafficking, suggesting a link between EGFR trafficking and neuroblastoma pathogenesis. We have analyzed the role of UBE4B in the EGFR pathway in neuroblastoma cell lines. Methods: The expression of UBE4B, hrs and EGFR were analyzed by quantitative Western blot in a panel of 7 human neuroblastoma cell lines (SHEP, SKNAS, SKNSH, KCNR, SY5Y, LA155N, NGP). EGFR degradation rates were determined by examining the kinetics of cellular EGFR depletion following a pulse of ligand. Results: UBE4B levels were lowest in SKNAS and highest in NGP cells. Hrs levels were lowest in SKNSH cells and higher in other cell lines. ...