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NSCLC and the alternative pathway of NF-κB: uncovering an unknown relation

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Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. Although our knowledge on the pathobiology of the disease has increased in the last decades, the prognosis of lung cancer patients has hardly changed. Many signaling pathways are implicated in lung carcinogenesis, but the role of the alternative pathway of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in lung cancer pathogenesis and progression has not been investigated. The aim of our study was to investigate the role of this pathway in non-small cell lung cancer (NSCLC) patients. NF-κB2 and RelB protein expression was retrospectively assessed by immunohistochemistry in tissue samples from 109 NSCLC patients. RelB and NF-κB2 protein levels differed between tumors and adjacent nonneoplastic lung parenchyma. Cytoplasmic immunoreactivity of NF-κB2 and RelB was correlated with tumor stage (p = 0.03 and p = 0.016, respectively). In addition, cytoplasmic NF-κB2 levels were related to tumor grade (p = 0.046). Expression of RelB in the cytoplasm was tumor histologic type-specific, with squamous cell carcinomas having the highest protein levels. Nuclear expression of RelB and NF-κB2 differed between tumor and nonneoplastic tissues, possibly indicating activation of the alternative pathway of NF-κB in cancer cells. Moreover, lymph node metastasis was related to nuclear NF-κB2 expression in tumor cells. The deregulation of the alternative NF-κB pathway in NSCLC could play a role in the development and progression of the disease.

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Acknowledgments

This research has been co-financed by the European Union (European Social Fund–ESF) and Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF)–Research Funding Program: Heracleitus II. Investing in knowledge society through the European Social Fund.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Molecular Oncology Laboratory, Division of Oncology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece

    Fotinos-Ioannis D. Dimitrakopoulos, Anna G. Antonacopoulou, Anastasia Kottorou & Haralabos P. Kalofonos

  2. Department of Pathology, Medical School, University of Patras, Patras, Greece

    Helen Vlotinou & Chrisoula Scopa

  3. Department of Cardiothoracic Surgery, Medical School, University of Patras, Patras, Greece

    Nikolaos D. Panagopoulos & Dimitrios Dougenis

  4. Department of Anatomy, Medical School, University of Patras, Patras, Greece

    Helen Papadaki

  5. Division of Oncology, Department of Medicine, Medical School, University of Patras, Rion, Patras, 26504, Greece

    Haralabos P. Kalofonos

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  1. Fotinos-Ioannis D. Dimitrakopoulos
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  2. Anna G. Antonacopoulou
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  3. Anastasia Kottorou
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  9. Haralabos P. Kalofonos
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Correspondence to Haralabos P. Kalofonos.

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Dimitrakopoulos, FI.D., Antonacopoulou, A.G., Kottorou, A. et al. NSCLC and the alternative pathway of NF-κB: uncovering an unknown relation. Virchows Arch 460, 515–523 (2012). https://doi.org/10.1007/s00428-012-1230-2

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  • DOI: https://doi.org/10.1007/s00428-012-1230-2

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