Cross-talk between EZH2 and NF-kB in breast cancers.

• Main Author: Ong, Sandy Li Ya.
• Other Authors: School of Biological Sciences
• Format: Final Year Project
• Language: English
• Published: 2010
• Subjects: DRNTU::Science::Biological sciences::Genetics
• Online Access: http://hdl.handle.net/10356/38681
• Institution: Nanyang Technological University

Epigenetic changes are reported to contribute to cancer progression. EZH2 is the catalytic component of PRC2 and its SET domain is involved in histone methyltransferase activity, to silence specific genes in cancer progression. Although EZH2 SET domain independent functions have been reported recently, it still remains novel and under-characterized in the aggressive breast cancer. Correspondingly, NF-κB is constitutively active in breast cancer. As many target genes of NF-κB family of transcription factors are involved in cancer progression, inflammation and tumorigenesis, it remains unknown if EZH2 plays a role in activating some of the target genes by modulating NF-κB activity. In this study, MDA-MB231 and BT549 aggressive breast carcinoma cell lines were used to investigate the functional interaction between EZH2 and NF-κB and it was found that EZH2 physically interacts with RelB to maintain stability of the latter. Over-expression of EZH2 WT and EZH2 SET∆ increases the relative mRNA expression of TNFα, suggesting that EZH2 is required to interact with RelB in a SET domain independent way to induce transcriptional activation of TNFα. Over-expression of EZH2 in aggressive breast cancer might therefore set up a vicious cycle by increasing TNFα-induced NF-κB activation and ultimately the transcription of target genes involved in inflammation and tumorigenesis.