Abstract
The NF-κB2/p100 and bcl-3 genes are involved in chromosomal translocations described in chronic lymphocytic leukemias (CLL) and non-Hodgkin's lymphomas, and nuclear factor kappaB (NF-κB) protects cancer cells against apoptosis. Therefore, we investigated whether this transcription factor could modulate the expression of the Bcl-2 antiapoptotic protein. Bcl-2 promoter analysis showed multiple putative NF-κB binding sites. Transfection assays of bcl-2 promoter constructs in HCT116 cells showed that NF-κB can indeed transactivate bcl-2. We identified a κB site located at position −180 that can only be bound and transactivated by p50 or p52 homodimers. As p50 and p52 homodimers are devoid of any transactivating domains, we showed that they can transactivate the bcl-2 promoter through association with Bcl-3. We also observed that stable overexpression of p100 and its processed product p52 can induce endogenous Bcl-2 expression in MCF7AZ breast cancer cells. Finally, we demonstrated that, in breast cancer and leukemic cells (CLL), high NF-κB2/p100 expression was associated with high Bcl-2 expression. Our data suggest that Bcl-2 could be an in vivo target gene for NF-κB2/p100.
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Acknowledgements
We thank Dr U Siebenlist (NIH, Bethesda, MD, USA) for his helpful comments on the manuscript, Dr L Boxer (Stanford, CA, USA) for the Bcl-2 Luc plasmids, Dr Hagemeijer (Leuven, Belgium) and Dr Lambert (CHU Liège, Belgium) for CLL samples. We are most thankful to Professor J Gielen (University of Liège, Belgium) for his continuous support during this work. M-P Merville, A Chariot and L de Leval are Research Associates at the National Foundation for Scientific Research (FNRS, Belgium). P Viatour, M Bentires-Alj and V Deregowski are supported by Télévie fellowships (FNRS, Belgium). This research was supported by grants from the ‘Centre Anti-Cancéreux’ (University of Liège, Belgium) and the FRSM (FNRS, Belgium).
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Viatour, P., Bentires-Alj, M., Chariot, A. et al. NF-κB2/p100 induces Bcl-2 expression. Leukemia 17, 1349–1356 (2003). https://doi.org/10.1038/sj.leu.2402982
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DOI: https://doi.org/10.1038/sj.leu.2402982
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