Abstract
Epstein-Barr virus (EBV) transforms B-l/mphocytes into lymphoblastoid cell lines usurping multiple signaling pathways including NF-κB activation. To determine whether NF-κB activity is essential in the growth and survival of EBV-transformed lymphoblastoid cell lines, a non-degradable IκBa mutant was expressed under tetracycline regulation in IB4 cells. NF-κB inhibition caused caspase 3 and 8 activation, PARP cleavage, and DNA fragmentation indicative of apoptosis. Mitochondrial membrane potential was diminished without release of cytochrome c or apoptosis initiating factor. z-VAD.FMK, a general caspase inhibitor, failed to block apoptosis, indicating a distinct pathway contributes to cell death. Bfl-1 expression, an anti-apoptotic Bcl–2 family member, is diminished after NF-κB inhibition whereas Bcl–2 and Bcl-x/L expression is unaffected. These studies suggest that NFκB itself, or NF-κB-regulated genes, will be successful molecular targets for the treatment of EBV-associated diseases.
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Cahir-McFarland, E., Kieff, E. (2002). NF-κB Inhibition in EBV-Transformed Lymphoblastoid Cell Lines. In: Oertel, S.H., Riess, H. (eds) Immunosurveillance, Immunodeficiencies and Lymphoproliferations. Recent Results in Cancer Research, vol 159. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56352-2_6
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DOI: https://doi.org/10.1007/978-3-642-56352-2_6
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