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High expression of RelA/p65 is associated with activation of nuclear factor-kappaB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis

Item Type:Article
Title:High expression of RelA/p65 is associated with activation of nuclear factor-kappaB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis
Creators Name:Weichert, W. and Boehm, M. and Gekeler, V. and Bahra, M. and Langrehr, J. and Neuhaus, P. and Denkert, C. and Imre, G. and Weller, C. and Hofmann, H.P. and Niesporek, S. and Jacob, J. and Dietel, M. and Scheidereit, C. and Kristiansen, G.
Abstract:Activation of nuclear factor-kappaB (NF-kappaB) signaling was observed in pancreatic adenocarcinoma cell lines and tumours. However, information on the expression of RelA/p65, the major transcription activating NF-kappaB subunit, in these carcinomas and possible correlations thereof with NF-kappaB activation and patient survival is not available. To provide this missing translational link, we analysed expression of RelA/p65 in 82 pancreatic adenocarcinomas by immunohistochemistry. Moreover, we measured activation of the NF-kappaB pathway in 11 tumours by quantitative PCR for NF-kappaB target genes. We observed strong cytoplasmic or nuclear expression of RelA/p65 in 42 and 37 carcinomas, respectively. High cytoplasmic and nuclear expression of RelA/p65 had negative prognostic impact with 2-year survival rates for patients without cytoplasmic or nuclear RelA/p65 positivity of 41 and 40% and rates for patients with strong cytoplasmic or nuclear RelA/p65 expression of 22 and 20%, respectively. High RelA/p65 expression was correlated to increased expression of NF-kappaB target genes. The observation that high expression of RelA/p65 is correlated to an activation of the NF-kappaB pathway and indicates poor patient survival identifies a patient subgroup that might particularly benefit from NF-kappaB-inhibiting agents in the treatment of pancreatic cancer. Based on our findings, this subgroup could be identified by applying simple immunohistochemical techniques.
Keywords:NF-kappaB, Pancreatic carcinoma, RelA, Prognosis, Survival, Immunohistochemistry
Source:British Journal of Cancer
ISSN:0007-0920
Publisher:Nature Publishing Group (U.K.)
Volume:97
Page Range:523-530
Date:14 August 2007
Official Publication:https://doi.org/10.1038/sj.bjc.6603878
PubMed:View item in PubMed

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