title: NSCLC and the alternative pathway of NF-κB: uncovering an unknown relation.
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.
authors.affiliation: Molecular Oncology Laboratory, Division of Oncology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece.
authors.forename: Fotinos-Ioannis D
authors.initials: FI
authors.lastname: Dimitrakopoulos
authors.forename: Anna G
authors.initials: AG
authors.lastname: Antonacopoulou
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kottorou
authors.forename: Helen
authors.initials: H
authors.lastname: Vlotinou
authors.forename: Nikolaos D
authors.initials: ND
authors.lastname: Panagopoulos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Dougenis
authors.forename: Chrisoula
authors.initials: C
authors.lastname: Scopa
authors.forename: Helen
authors.initials: H
authors.lastname: Papadaki
authors.forename: Haralabos P
authors.initials: HP
authors.lastname: Kalofonos
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015398:Signal Transduction / Q000502:physiology*; D051841:Transcription Factor RelB / Q000378:metabolism
chemical_list: D016328:NF-kappa B; C497593:RELB protein, human; D051841:Transcription Factor RelB