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Abstract 4535: CENP-E and c-Myc expression identifies a sensitive population of gastric cancer

Centromere-associated protein E (CENP-E) is expressed during mitosis and plays an essential role in establishing and maintaining stable connections between mitotic chromosomes and the microtubules of the spindle. Previous preclinical studies have shown that inhibition of CENP-E function by small int...

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Published in:Cancer research (Chicago, Ill.) Ill.), 2012-04, Vol.72 (8_Supplement), p.4535-4535
Main Authors: Li, Gang, Fan, Conglin, Deng, Shibing, Xu, Jiangchun, Shi, Stephanie, Wang, Kai, Pascual, Bernadette, Kung, Pei-Pei, Leung, Suet Yi, Yue, Siu Tsan
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container_issue 8_Supplement
container_start_page 4535
container_title Cancer research (Chicago, Ill.)
container_volume 72
creator Li, Gang
Fan, Conglin
Deng, Shibing
Xu, Jiangchun
Shi, Stephanie
Wang, Kai
Pascual, Bernadette
Kung, Pei-Pei
Leung, Suet Yi
Yue, Siu Tsan
description Centromere-associated protein E (CENP-E) is expressed during mitosis and plays an essential role in establishing and maintaining stable connections between mitotic chromosomes and the microtubules of the spindle. Previous preclinical studies have shown that inhibition of CENP-E function by small interfering RNA, blocking antibodies or small molecule inhibitors arrested cell cycle before metaphase, and could lead to cell death. In a number of cancers, CENP-E is frequently overexpressed in tumor tissues compared with their normal counterparts. In this study, we showed that CENP-E is overexpressed in about 60% of gastric cancer (intestinal and diffuse-type) tissues. In addition, c-Myc up-regulation was observed in more than 50% of the same samples. Overall, about 40% of all gastric tumor samples harbor both CENP-E and c-Myc upregulation. Using a panel of small molecule inhibitors of CENP-E, we evaluated in vitro anti-proliferation effect in a panel of gastric cancer cell lines. Our data suggested that cells with higher levels of c-Myc transcript were more sensitive to CENP-E inhibition. This preliminary study indicated that c-Myc amplification and/or over-expression could be a potential biomarker for selecting gastric cancer patients more likely to respond to CENP-E inhibition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4535. doi:1538-7445.AM2012-4535
doi_str_mv 10.1158/1538-7445.AM2012-4535
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Previous preclinical studies have shown that inhibition of CENP-E function by small interfering RNA, blocking antibodies or small molecule inhibitors arrested cell cycle before metaphase, and could lead to cell death. In a number of cancers, CENP-E is frequently overexpressed in tumor tissues compared with their normal counterparts. In this study, we showed that CENP-E is overexpressed in about 60% of gastric cancer (intestinal and diffuse-type) tissues. In addition, c-Myc up-regulation was observed in more than 50% of the same samples. Overall, about 40% of all gastric tumor samples harbor both CENP-E and c-Myc upregulation. Using a panel of small molecule inhibitors of CENP-E, we evaluated in vitro anti-proliferation effect in a panel of gastric cancer cell lines. Our data suggested that cells with higher levels of c-Myc transcript were more sensitive to CENP-E inhibition. This preliminary study indicated that c-Myc amplification and/or over-expression could be a potential biomarker for selecting gastric cancer patients more likely to respond to CENP-E inhibition. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. 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