Expression of c-src in cultured human neuroblastoma and small-cell lung carcinoma cell lines correlates with neurocrine differentiation.
Human cell lines with neuronal and neuroendocrine features were examined for their expression of pp60c-src, the cellular homolog of the transforming gene product pp60v-src of Rous sarcoma virus. Four neuroblastoma (LA-N-5, SH-SY5Y, Paju, and SK-N-MC) and three small-cell lung carcinoma (U-2020, U-1690, and U-1285) cell lines were selected on the basis of their stage of neurocrine differentiation, as determined by the expression of neuron-specific enolase. In an immune complex protein kinase assay, all seven cell lines displayed c-src kinase activity which was considerably higher than that found in nonneurocrine cells (human diploid fibroblasts, glioma, and non-small cell lung carcinoma cell lines). Furthermore, the c-src kinase activity, as determined by autophosphorylation or phosphorylation of an exogenous substrate, enolase, correlated with the stage of neurocrine differentiation. There was an approximately 30-fold difference in c-src kinase autophosphorylation activity between the cell lines representing the highest and lowest stages of neurocrine differentiation. A similar variation was found in the steady-state levels of the c-src protein of these cell lines. Highly differentiated neuroblastoma cells expressed two forms of the src protein. Digestion by Staphylococcus aureus V8 protease did reveal structural diversity in the amino-terminal ends of these c-src molecules. In summary, we found a clear correlation between c-src kinase activity and the stage of neuronal and neuroendocrine differentiation. Thus, the phenotypic similarity between neurons and neuroendocrine cells includes high c-src expression.
Mellström
K
K
Department of Pathology, University of Uppsala, Sweden.
Bjelfman
C
C
Hammerling
U
U
Påhlman
S
S
D018288:Carcinoma, Small Cell / Q000235:genetics*; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics*; D009474:Neurons / Q000378:metabolism; D015688:Oncogene Protein pp60(v-src); D009857:Oncogenes; D010641:Phenotype; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D012191:Retroviridae Proteins / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D012191:Retroviridae Proteins; D011494:Protein Kinases; D015688:Oncogene Protein pp60(v-src); D010751:Phosphopyruvate Hydratase