Abstract
Overexpression of the anti-apoptotic protein BCL-2 is frequently observed in small cell lung cancers (SCLC) and is associated with chemoresistance. We examined the signaling pathways involved in upregulation of BCL-2 in SCLC, and whether inhibition of NF-κB using the 26S proteasome inhibitor bortezomib had any effect on BCL-2 levels or apoptosis. Mutation of a NF-κB site in the BCL-2 promoter reduced promoter activity to less than 20% of the wild-type promoter. Treatment with bortezomib resulted in decreased transcription of the BCL-2 promoter, decreased BCL-2 levels, and induced apoptosis. These data provide the necessary laboratory background for further investigation of bortezomib in the treatment of SCLC.
Original language | English (US) |
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Pages (from-to) | 163-170 |
Number of pages | 8 |
Journal | Lung Cancer |
Volume | 49 |
Issue number | 2 |
DOIs | |
State | Published - Aug 2005 |
Keywords
- BCL-2
- Bortezomib
- NF-κB
- SCLC
ASJC Scopus subject areas
- Oncology