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 Nånberg; S Påhlman

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

Cell Growth Differ. 1995 Jun;6(6):727-36.

Authors

E Lavenius¹, C Gestblom, I Johansson, E Nånberg, S Påhlman

Affiliation

¹ Department of Pathology, University of Uppsala, University Hospital, Sweden.

PMID: 7669728

Abstract

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Cell Differentiation / drug effects
Gene Expression Regulation, Neoplastic / drug effects
Humans
Neoplasm Proteins / biosynthesis
Neoplasm Proteins / genetics
Nerve Growth Factors / pharmacology*
Neuroblastoma / pathology*
Phosphorylation / drug effects
Protein Processing, Post-Translational / drug effects
Proto-Oncogene Mas
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-fos / biosynthesis
Proto-Oncogene Proteins c-fos / genetics
Proto-Oncogenes
Receptor Protein-Tyrosine Kinases / genetics*
Receptor Protein-Tyrosine Kinases / metabolism
Receptor, trkA
Receptors, Nerve Growth Factor / genetics*
Receptors, Nerve Growth Factor / metabolism
Recombinant Fusion Proteins / metabolism
Transfection
Tumor Cells, Cultured

Substances

MAS1 protein, human
Neoplasm Proteins
Nerve Growth Factors
Proto-Oncogene Mas
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-fos
Receptors, Nerve Growth Factor
Recombinant Fusion Proteins
Receptor Protein-Tyrosine Kinases
Receptor, trkA