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Oncogene. 2013 Mar 21;32(12):1601-8. doi: 10.1038/onc.2012.175. Epub 2012 May 14.

Expression of Id proteins is regulated by the Bcl-3 proto-oncogene in prostate cancer.

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1
Center for Molecular Tumor Pathology, Department of Laboratory Medicine, Lund University, Skåne University Hospital, Malmö, Sweden.

Abstract

B-cell leukemia 3 (Bcl-3) is a member of the inhibitor of κB family, which regulates a wide range of biological processes by functioning as a transcriptional activator or as a repressor of target genes. As high levels of Bcl-3 expression and activation have been detected in different types of human cancer, Bcl-3 has been labeled a proto-oncogene. Our study uncovered a markedly upregulated Bcl-3 expression in human prostate cancer (PCa), where inflammatory cell infiltration was observed. Elevated Bcl-3 expression in PCa was dependent on the proinflammatory cytokine interleukin-6-mediated STAT3 activation. Microarray analyses, using Bcl-3 knockdown in PCa cells, identified the inhibitor of DNA-binding (Id) family of helix-loop-helix proteins as potential Bcl-3-regulated genes. Bcl-3 knockdown reduced the abundance of Id-1 and Id-2 proteins and boosted PCa cells to be more receptive to undergoing apoptosis following treatment with anticancer drug. Our data imply that inactivation of Bcl-3 may lead to sensitization of cancer cells to chemotherapeutic drug-induced apoptosis, thus suggesting a potential therapeutic strategy in PCa treatment.

PMID:
22580608
DOI:
10.1038/onc.2012.175
[Indexed for MEDLINE]

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