Novel actions of tyrphostin AG 879: inhibition of RAF-1 and HER-2 expression combined with strong antitumoral effects on breast cancer cells
| Autor: | Larsson Li |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Time Factors
animal structures Receptor ErbB-2 Immunoblotting MAPK7 Antineoplastic Agents Apoptosis Breast Neoplasms Biology Mitogen-activated protein kinase kinase MAP2K7 Cellular and Molecular Neuroscience Cell Line Tumor Humans Immunoprecipitation ASK1 c-Raf Enzyme Inhibitors Molecular Biology Cell Proliferation Pharmacology Dose-Response Relationship Drug MAP kinase kinase kinase Reverse Transcriptase Polymerase Chain Reaction Cyclin-dependent kinase 4 Tyrphostin AG 879 Cell Biology Tyrphostins Proto-Oncogene Proteins c-raf Cancer research biology.protein Molecular Medicine Electrophoresis Polyacrylamide Gel Signal Transduction |
| Zdroj: | Cellular and Molecular Life Sciences. 61:2624-2631 |
| ISSN: | 1420-9071 1420-682X |
| DOI: | 10.1007/s00018-004-4279-5 |
| Popis: | Binding of growth factors to cell surface receptors activates protein tyrosine kinases (PTKs) that initiate cascades of downstream signaling events including the mitogen-activated protein (MAP) kinase cascade. This study reports that the PTK inhibitor AG 879 inhibits proliferation of human breast cancer cells through an effect involving inhibition of MAP kinase activation, but which cannot be explained by effects of AG 879 on its known PTK targets. Instead, AG 879 markedly inhibits expression of the RAF-1 gene, which encodes an upstream MAP kinase kinase kinase. Additionally, expression of HER-2, but not of other genes tested, is inhibited by this compound. These novel effects have to be considered when using AG 879 as a TRK-A and HER-2 inhibitor but may have useful therapeutic implications. |
| Databáze: | OpenAIRE |
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