Abstract
Abstract Bcl-3 is an oncogene first identified by its translocation into the immunoglobulin alpha-locus in some cases of chronic B cell lymphocytic leukemia. Bcl-3 is an atypical member of the IκB family that exhibits unique properties compared with classic IκBs. It readily enters nuclei, where it interacts with p50/NF-κB1 or p52/NF-κB2 homodimers to transcriptional activity. Depending on the cellular context and target gene, Bcl-3 may promote or inhibit gene expression. Recently it was reported that Bcl-3 could promote tumor growth as well as metastasis in several mouse tumor models. Bcl-3 is also known to play important roles in innate and adaptive immunity. For example, mice lacking Bcl-3 become highly susceptible to various pathogens, including T. gondii and K. pneumoniae, but the underlying mechanisms remain poorly understood. In addition, little is known about potential roles of Bcl-3 in inflammation that may contribute to cancers. Here we report that in a mouse model of colitis, which is dependent on the functions of Th1 cells, Bcl-3 had an intrinsic role to maintain Th1 cells and thus promote inflammation over time. This could also be demonstrated in vitro, where Bcl-3 had no effect on differentiation of Th1 cells per se, but was required for their maintenance. We will show how Bcl-3 promoted the maintenance of specifically Th1, but not Th17 cells. We will also provide evidence that Bcl-3 likely mediated these effects via p52/NF-κB2. Our data demonstrate that the oncoprotein Bcl-3 can contribute to chronic inflammatory conditions that in turn may be associated with cancer development. Note: This abstract was not presented at the meeting. Citation Format: Wanhu Tang, Hongshan Wang, Estefania Claudio, Ulrich Siebenlist. The pro-inflammatory role of the putative oncogene Bcl-3. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1661. doi:10.1158/1538-7445.AM2014-1661
Published Version
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