Receptor tyrosine kinase AXL is induced by chemotherapy drugs and overexpression of AXL confers drug resistance in acute myeloid leukemia
| Autor: | Shuang En Chuang, Jong Ding Lay, Ming Tseh Lin, Jhy Shrian Huang, Ann-Lii Cheng, Jih-Luh Tang, Chih Chen Hong, Gi Ming Lai |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Myeloid Molecular Sequence Data Antineoplastic Agents Receptor tyrosine kinase Proto-Oncogene Proteins hemic and lymphatic diseases Humans Medicine Promoter Regions Genetic Protein kinase B Oncogene Proteins Base Sequence AXL receptor tyrosine kinase biology GAS6 business.industry Receptor Protein-Tyrosine Kinases Myeloid leukemia U937 Cells medicine.disease Axl Receptor Tyrosine Kinase Leukemia Myeloid Acute Leukemia medicine.anatomical_structure Oncology Drug Resistance Neoplasm biology.protein Cancer research Intercellular Signaling Peptides and Proteins Phosphorylation business Signal Transduction |
| Zdroj: | Cancer Letters. 268:314-324 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/j.canlet.2008.04.017 |
| Popis: | By using a novel profiling analysis of protein tyrosine kinases differentially expressed in the sensitive and refractory leukemia from the same patients we found that AXL was upregulated in drug-resistant leukemia. Furthermore, AXL could be induced by chemotherapy drugs in the acute myeloid leukemia U937 cells and this induction was dependent on the CCWGG methylation status of the AXL promoter. In U937 cells ectopically overexpressing AXL, addition of exogenous Gas6 induced AXL phosphorylation and activation of the Akt and ERK1/2 survival pathways. The Gas6-AXL activation pathway of drug resistance was associated with increased expression of Bcl-2 and Twist. These results show that upregulation of AXL by chemotherapy might induce drug resistance in acute myeloid leukemia in the presence of Gas6 stimulation. |
| Databáze: | OpenAIRE |
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