Reduction in BCL-2 levels by 26S proteasome inhibition with bortezomib is associated with induction of apoptosis in small cell lung cancer

Melinda M. Mortenson; Michael G. Schlieman; Subbulakshmi Virudachalam; Primo N Lara; David R Gandara; Angela M. Davies; Richard J Bold

doi:10.1016/j.lungcan.2005.01.006

Reduction in BCL-2 levels by 26S proteasome inhibition with bortezomib is associated with induction of apoptosis in small cell lung cancer

Melinda M. Mortenson, Michael G. Schlieman, Subbulakshmi Virudachalam, Primo N Lara, David R Gandara, Angela M. Davies, Richard J Bold

Research output: Contribution to journal › Article › peer-review

42 Scopus citations

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	https://doi.org/10.1016/j.lungcan.2005.01.006
State	Published - Aug 2005

Keywords

BCL-2
Bortezomib
NF-κB
SCLC

ASJC Scopus subject areas

Oncology

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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 › peer-review

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title = "Reduction in BCL-2 levels by 26S proteasome inhibition with bortezomib is associated with induction of apoptosis in small cell lung cancer",

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.",

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AU - Gandara, David R

AU - Davies, Angela M.

AU - Bold, Richard J

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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.

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