Upregulation of Bcl-x and Bfl-1 as a potential mechanism of chemoresistance, which can be overcome by NF-[kappa]B inhibition
In A549 human lung adenocarcinoma cells, we found that TNF-alpha and several commonly used chemotherapeutic agents upregulated the expression of Bcl-x and/or Bfl-1/A1 through an NF-kappaB-dependent pathway. While parental A549 cells were resistant to the cytotoxic effects of both TNF-alpha and chemo...
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| Published in: | Oncogene Vol. 19; no. 42; p. 4936 |
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| Main Authors: | , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
New York
Nature Publishing Group
05-10-2000
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| Online Access: | Get full text |
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| Summary: | In A549 human lung adenocarcinoma cells, we found that TNF-alpha and several commonly used chemotherapeutic agents upregulated the expression of Bcl-x and/or Bfl-1/A1 through an NF-kappaB-dependent pathway. While parental A549 cells were resistant to the cytotoxic effects of both TNF-alpha and chemotherapy agents, NF-kappaB-blocked A549 cells were sensitized to both. Expression of either Bcl-x or Bfl-1/A1 in the NF-kappaB-deficient cells at physiological levels provided differential protection against TNF-alpha and chemotherapeutic treatment. These studies provide a potential mechanism for the phenomenon of chemotherapy-induced chemoresistance, and also reveal a potential strategy by which chemoresistance can be overcome. |
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| ISSN: | 0950-9232 1476-5594 |
| DOI: | 10.1038/sj.onc.1203861 |