Abstract
The induction of growth inhibition and differentiation of a glioma cell line by transfection of trk A cDNA was examined, and production of endogenous nerve growth factor (NGF) also was studied in these cells. When human trk A cDNA was transfected into a human glioma cell line, U-251MG, which lacks expression of both endogenous trk A and low-affinity NGF receptor, the transfectant expressed the exogenous trk A mRNA and a functional high-affinity NGF receptor. Transfection of trk A cDNA caused a partial induction of cell differentiation, G1 arrest, growth inhibition, tyrosine phosphorylation of the trk A proto-oncogene product, and activation of MAP kinase. Exogenous NGF treatment induced further terminal differentiation and growth inhibition. In summary, our data suggest that endogenous NGF secreted by glioma cells has an important role in the induction of glioma-cell differentiation occuring with transfer of exogenous trk A cDNA.
MeSH terms
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Animals
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Brain Neoplasms / pathology*
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Cell Cycle
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Cell Differentiation
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Cell Division
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Cerebellar Neoplasms / pathology
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DNA, Complementary
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Genes, fos
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Glial Fibrillary Acidic Protein / analysis
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Glial Fibrillary Acidic Protein / genetics
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Glioma / pathology*
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Humans
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Kinetics
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Medulloblastoma / pathology
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Mice
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Mice, SCID
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Nerve Growth Factors / genetics
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Proto-Oncogene Mas
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism*
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Receptor Protein-Tyrosine Kinases / genetics*
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Receptor Protein-Tyrosine Kinases / metabolism*
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Receptor, trkA
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Receptors, Nerve Growth Factor / genetics*
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Receptors, Nerve Growth Factor / metabolism*
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Recombinant Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription, Genetic*
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Transfection
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Transplantation, Heterologous
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Tumor Cells, Cultured
Substances
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DNA, Complementary
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Glial Fibrillary Acidic Protein
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MAS1 protein, human
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Nerve Growth Factors
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Proto-Oncogene Mas
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Proto-Oncogene Proteins
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Receptors, Nerve Growth Factor
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Recombinant Proteins
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Receptor Protein-Tyrosine Kinases
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Receptor, trkA