Cell Growth & Differentiation, Vol 6, Issue 6 727-736, Copyright © 1995 by American Association of Cancer Research

ARTICLES

Transfection of TRK-A into human neuroblastoma cells restores their ability to differentiate in response to nerve growth factor

E Lavenius, C Gestblom, I Johansson, E Nanberg and S Pahlman
Department of Pathology, University of Uppsala, University Hospital, Sweden.

Human neuroblastoma cell lines frequently express the TRK-A proto-oncogene and bind nerve growth factor (NGF) but do not differentiate when exposed to NGF. Transient transfection of an exogenous TRK-A gene into SH-SY5Y and LA-N-5 neuroblastoma cells restored the ability of these tumor cells to differentiate with NGF. Stable TRK-A-transfected SH-SY5Y cell clones were isolated, and they responded to NGF by autophosphorylation of p140trk-A, c-fos induction, morphological differentiation, and increased expression of two neuronal marker genes, neuropeptide tyrosine and GAP-43. In phorbol ester-induced differentiated wild-type cells, TRK-A expression was increased with no change in NGF responsiveness. Thus, the restoration of the NGF-induced differentiation pathway by exogenous TRK-A presents a system of NGF-responsive human cultured cells and focuses attention on the trk-A protein and its function or malfunction in neuroblastoma.

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