Abstract
Bortezomib (PS-341), a selective inhibitor of proteasome, induces apoptosis in various tumor cells, but its mechanism of action is unclear. Treatment with PS-341 induces apoptosis in SUDHL6 (DHL6), but not SUDHL4 (DHL4), lymphoma cells. Microarray analysis shows high RNA levels of heat shock protein-27 (Hsp27) in DHL4 versus DHL6 cells, which correlates with Hsp27 protein expression. Blocking Hsp27 using an antisense strategy restores the apoptotic response to PS-341 in DHL4 cells; conversely, ectopic expression of wild-type Hsp27 renders PS-341-sensitive DHL6 cells resistant to PS-341. These findings provide the first evidence that Hsp27 confers PS-341 resistance.
| Original language | English |
|---|---|
| Pages (from-to) | 6174-6177 |
| Number of pages | 4 |
| Journal | Cancer Research |
| Volume | 63 |
| Issue number | 19 |
| Publication status | Published - 01 Oct 2003 |
| Externally published | Yes |
Keywords
- Apoptosis/drug effects
- Boronic Acids/pharmacology
- Bortezomib
- Cell Line, Tumor
- Cell Survival/drug effects
- Cysteine Endopeptidases
- Drug Resistance, Neoplasm
- HSP27 Heat-Shock Proteins
- Heat-Shock Proteins
- Humans
- Leupeptins/pharmacology
- Lymphoma/drug therapy
- Molecular Chaperones
- Multienzyme Complexes/antagonists & inhibitors
- Neoplasm Proteins/antagonists & inhibitors
- Proteasome Endopeptidase Complex
- Pyrazines/pharmacology
- RNA, Messenger/genetics
- Transfection