Effect of tyrphostin on cell growth and tyrosine kinase activity of epidermal growth factor receptor in human gliomas
| Autor: | Takashi Tokunaga, Eiichi Tani, Hideki Shindo, Katsuya Miyaji, Atsuhisa Nakano |
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| Rok vydání: | 1994 |
| Předmět: |
Catechols
Down-Regulation Tropomyosin receptor kinase C Receptor tyrosine kinase chemistry.chemical_compound Epidermal growth factor Nitriles Tumor Cells Cultured Humans Epidermal growth factor receptor Dose-Response Relationship Drug Epidermal Growth Factor biology Cell growth Tyrosine phosphorylation Glioma Protein-Tyrosine Kinases Tyrphostins ErbB Receptors Kinetics chemistry Cancer research biology.protein Tyrosine kinase Cell Division hormones hormone substitutes and hormone antagonists Platelet-derived growth factor receptor |
| Zdroj: | Journal of Neurosurgery. 81:411-419 |
| ISSN: | 0022-3085 |
| DOI: | 10.3171/jns.1994.81.3.0411 |
| Popis: | ✓ The effects of tyrphostin, a selective protein tyrosine kinase inhibitor, on epidermal growth factor (EGF)-stimulated cell growth and EGF-receptor tyrosine kinase activity were studied in four human glioma cell lines. Stimulation by EGF induced variable enhancements of cell growth as well as tyrosine phosphorylation of EGF receptor and intracellular target proteins in all glioma cell lines. The level of immunoreactive EGF receptor detected with antibodies against extra- and intracellular domains was moderate in all four glioma cell lines, but markedly decreased with the latter antibody in two glioma cell lines. This variation was associated with considerable reduction of the EGF-stimulated tyrosine autophosphorylation level. Tyrphostin inhibited dose-dependently the EGF-stimulated cell growth and tyrosine autophosphorylation in all glioma cell lines, and the optimum time for the maximum inhibitory effect on tyrosine autophosphorylation was 12 to 18 hours after treatment with tyrphostin. The antiproliferative activity of tyrphostin nearly correlated quantitatively with its potency as an inhibitor of the EGF-stimulated EGF receptor tyrosine kinase activity. Tyrphostin had no significant effect on the immunoreactive EGF receptor levels, on the affinity constants and numbers of EGF receptor, or on the down-regulation and specific internalization of EGF receptor in any glioma cell line, suggesting that the effects of tyrphostin are not likely to be the results of reduction in EGF receptor and EGF binding capacity. In addition, the serum-stimulated cell growth was also inhibited dose-dependently by higher concentrations of tyrphostin in all glioma cell lines. It might be suggested, therefore, that tyrphostin inhibits EGF-stimulated cell growth by a specific suppression of EGF receptor tyrosine kinase activity, and at higher concentrations there appears to be some degree of either nonspecific inhibition or inhibition of serum-stimulated protein tyrosine kinase activity to induce the cell growth inhibition of gliomas. |
| Databáze: | OpenAIRE |
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