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 journalArticle

41 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)163-170
Number of pages8
JournalLung Cancer
Volume49
Issue number2
DOIs
StatePublished - Aug 2005

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Small Cell Lung Carcinoma
Apoptosis
Apoptosis Regulatory Proteins
Proteasome Inhibitors
Up-Regulation
Mutation
Bortezomib
ATP dependent 26S protease

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 journalArticle

Mortenson, Melinda M. ; Schlieman, Michael G. ; Virudachalam, Subbulakshmi ; Lara, Primo N ; Gandara, David R ; Davies, Angela M. ; Bold, Richard J. / Reduction in BCL-2 levels by 26S proteasome inhibition with bortezomib is associated with induction of apoptosis in small cell lung cancer. In: Lung Cancer. 2005 ; Vol. 49, No. 2. pp. 163-170.
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