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) |
|---|---|
| Pages (from-to) | 163-170 |
| Number of pages | 8 |
| Journal | Lung Cancer |
| Volume | 49 |
| Issue number | 2 |
| DOIs | |
| State | Published - Aug 2005 |
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Keywords
- BCL-2
- Bortezomib
- NF-κB
- SCLC
ASJC Scopus subject areas
- Oncology
Cite this
Reduction in BCL-2 levels by 26S proteasome inhibition with bortezomib is associated with induction of apoptosis in small cell lung cancer. / Mortenson, Melinda M.; Schlieman, Michael G.; Virudachalam, Subbulakshmi; Lara, Primo N; Gandara, David R; Davies, Angela M.; Bold, Richard J.
In: Lung Cancer, Vol. 49, No. 2, 08.2005, p. 163-170.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reduction in BCL-2 levels by 26S proteasome inhibition with bortezomib is associated with induction of apoptosis in small cell lung cancer
AU - Mortenson, Melinda M.
AU - Schlieman, Michael G.
AU - Virudachalam, Subbulakshmi
AU - Lara, Primo N
AU - Gandara, David R
AU - Davies, Angela M.
AU - Bold, Richard J
PY - 2005/8
Y1 - 2005/8
N2 - 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.
AB - 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.
KW - BCL-2
KW - Bortezomib
KW - NF-κB
KW - SCLC
UR - http://www.scopus.com/inward/record.url?scp=22044440019&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=22044440019&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2005.01.006
DO - 10.1016/j.lungcan.2005.01.006
M3 - Article
C2 - 16022909
AN - SCOPUS:22044440019
VL - 49
SP - 163
EP - 170
JO - Lung Cancer
JF - Lung Cancer
SN - 0169-5002
IS - 2
ER -