Abstract 3070: CHFR, a potential tumor suppressor, downregulates interleukin-8 via inhibition of NF-κB

Abstract

Abstract The mitoic checkpoint gene CHFR is silenced in various human cancers, suggesting that CHFR is a tumor suppressor. Here, we reveal that CHFR functions as a negative regulator of the NF-kB pathway. Expression of CHFR inhibited NF-kB reporter activity, while knockdown of CHFR activated reporter activity. These activities are independent of its RING finger domain. Further we found that CHFR interacts with p65 and negatively regulates transcriptional activity of p65. Moreover, our data demonstrate that IL-8 is significantly downregulated by CHFR and that the migration of human endothelial cells is suppressed in culture medium conditioned from CHFR-expressing cancer cells. Using a xenograft model, we show that angiogenesis is suppressed by adenovirus-mediated transfer of CHFR. These results indicate that expression of CHFR markedly reduces expression of IL-8 via the inhibition of NF-kB. Because the NF-kB plays a critical role in the development and progression of cancer, our finding demonstrate the functional relationship between epigenetic alteration and inflammation/antiogenesis in human cancer cells, thereby revealing several potential target for therapeutic intervention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3070.