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

Oncogene volume 32, pages 1601–1608 (2013)Cite this article

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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.

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Acknowledgements

We thank Elise Nilsson for excellent technical assistance, Dr Zoran Culig (Innsbruck Medical University, Austria) for providing us the LNCaP-IL-6+ cells, Dr Takashi Tokino (Cancer Research Institute, Sapporo, Japan) for human Id-2 promoter luciferase reporter construct, Dr Roland M Schmid (Technical University Munich, Munich, Germany) for FLAG-Bcl-3 expression construct, Dr David Ulmert (Lund University, Lund, Sweden) for characterization of the human PCa tissue microarray and Dr Srinivas Veerla (SCIBLU, Lund University, Lund, Sweden) for microarray analysis and gene expression profiling. This work was supported by the Swedish Society for Medical Research, Swedish Cancer Foundation, Swedish Medical Research Council, Royal Physiographic Society in Lund, U-MAS Research Foundations, and funding from the European Research Council under the European Union's seventh framework program ERC grant agreement (260460 to RM).

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Authors and Affiliations

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

    K Ahlqvist, K Saamarthy & R Massoumi

  2. Division of Urological Cancers, Department of Clinical Sciences, Lund University, Skåne University Hospital, Malmö, Sweden

    A S Syed Khaja & A Bjartell

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Correspondence to R Massoumi.

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Ahlqvist, K., Saamarthy, K., Syed Khaja, A. et al. Expression of Id proteins is regulated by the Bcl-3 proto-oncogene in prostate cancer. Oncogene 32, 1601–1608 (2013). https://doi.org/10.1038/onc.2012.175

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