| Autor: |
Gebauer G; Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA., Mirakhur B, Nguyen Q, Shore SK, Simpkins H, Dhanasekaran N |
| Jazyk: |
angličtina |
| Zdroj: |
International journal of oncology [Int J Oncol] 2000 Feb; Vol. 16 (2), pp. 321-5. |
| DOI: |
10.3892/ijo.16.2.321 |
| Abstrakt: |
Cisplatin has been widely used as a chemotherapeutic agent to treat different types of tumors. However, its use is limited by the ability of the tumor cells to develop cisplatin-resistance. The molecular lesion that produces cisplatin-resistance is poorly understood. In this report, we show that cisplatin activates a robust apoptotic pathway involving the activation of JNK and p38MAPK whereas it fails to elicit such a response in cisplatin-resistant 2008/C13 cells. Analysis of the defective apoptotic pathway in 2008/C13 cells indicates that these cells are deficient in the proteolytic activation of MEKK1 by caspase-3. The blunted activity of caspase-3 appears to be closely related to the increased levels of the anti-apoptotic protein Bcl-xL seen in the resistant cells. These studies, for the first time, demonstrate that inadequate caspase-3 processing and MEKK1 activation can lead to a drug-resistant phenotype. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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