Differentiation and Growth Inhibition of Glioma Cells Induced by Transfer of trk A Proto-oncogene

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.