Abstract
Overexpression of CD30 and constitutive NF-κB activation characterizes tumor cells of Hodgkin's disease (HD), Hodgkin and Reed-Sternberg (H–RS) cells. We report that in H–RS cells overexpression of CD30 leads to self-aggregation, recruitment of TRAF2 and TRAF5, and NF-κB activation, independent of CD30 ligand. CD30 and TRAF proteins co-localized in H–RS cell lines and in lymph nodes of HD. An adenovirus-vector carrying a decoy CD30 lacking the cytoplasmic region or a dominant negative IκBα mutant blocks NF-κB activation, down regulates IL-13 expression and induces apoptosis. Thus, in H–RS cells, ligand-independent activation of CD30 signaling drives NF-κB activation and this leads to constitutive cytokine expression, which provides a molecular basis for HD. Inhibition of NF-κB activation by adenovirus vector-mediated gene transfer may provide a novel strategy of cell- and target molecule-specific therapy for patients with HD.
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Acknowledgements
This work was supported in part by a Grant in Aid for Scientific Research and a Grant in Aid for Cancer Research from the Ministry of Education, Science, Technology, Sports and Culture, Japan, to T Watanabe, and by The Mochida Memorial Foundation for Medical and Pharmaceutical Research to R Horie. We thank M Ohara for comments on the manuscript.
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Horie, R., Watanabe, T., Morishita, Y. et al. Ligand-independent signaling by overexpressed CD30 drives NF-κB activation in Hodgkin–Reed-Sternberg cells. Oncogene 21, 2493–2503 (2002). https://doi.org/10.1038/sj.onc.1205337
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DOI: https://doi.org/10.1038/sj.onc.1205337
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