TrkA signal transduction pathways in neuroblastoma

✍ Scribed by Eggert, Angelika ;Ikegaki, Naohiko ;Liu, Xing-ge ;Chou, Tom T. ;Brodeur, Garrett M.

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 162 KB
• Volume: 36
• Category: Article
• ISSN: 0098-1532
• DOI: 10.1002/1096-911x(20010101)36:1<108::aid-mpo1025>3.0.co;2-2

✦ Synopsis

Background. Favorable neuroblastomas frequently express high levels of the TrkA receptor, and these tumors have a propensity to either differentiate or regress, but the mechanisms responsible for these two fates are unclear. Procedure. To study TrkA signal transduction in neuroblastoma (nb), we stably expressed wild-type TrkA and five TrkA mutants in the human nb cell line SH-SY5Y. Resulting single cell clones were characterized by TrkA mRNA and protein expression and by autophosphorylation of the receptor. Results. Introduction of TrkA restored nerve growth factor (NGF) responsiveness of SH-SY5Y cells, dem-onstrated by morphological differentiation and induction of immediate-early genes. TrkA overexpression leads to growth inhibition in theabsence of NGF, whereas NGF treatment results in increased proliferation. Conclusions. Analysis of downstream signaling elements in mutated TrkA receptors indicates that NGFinduced differentiation is dependent on TrkA kinase activity, but several redundant pathways seem to be used farther downstream. This suggests differences from TrkA pathways identified in PC12 cells.