Abstract 5086: BEX protein attenuates the mitotic checkpoint and induces preneoplastic aneuploidy

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The mitotic checkpoint plays a critical role in preventing chromosome missegregation and the adaptation of aneuploid cells. BubR1 kinase is a member of the mitotic checkpoint machinery. To understand the function of BubR1-mediated mitotic checkpoint, we have screened a novel BubR1-interating protein, BEX, by performing yeast two-hybrid systems. Here, we show that overexpression of BEX protein with sustained spindle poison results in a production of aneuploid cells and less apoptotic cell death. Inhibition of BubR1 expression increases aneuploid cell populations, whereas knockdown of both BEX and BubR1 avoid polyploidy by undergoing apoptosis in BubR1-depleted aneuploid cells. In addition, forced BEX expression significantly induces the colony forming potential and accelerates the proliferation rate. Interestingly, BEX is localized on X chromosome, and seems to be selectively expressed at cancer cells and tissues. These results indicate that BEX expression leads to mitotic dysfunction, and contributes to unstable chromosome aneuploid cells to be preneoplastically adapted. Citation Format: Jin-Kwan Lee, Geun-Hyoung Ha, Janet Lee, Chang-Woo Lee. BEX protein attenuates the mitotic checkpoint and induces preneoplastic aneuploidy. [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 5086. doi:10.1158/1538-7445.AM2014-5086