EWS-Fli1 Up-Regulates Expression of the Aurora A and Aurora B Kinases

被引：36
作者：
Wakahara, Kazuhiko [1 ]
Ohno, Takatoshi [1 ]
Kimura, Masashi [2 ]
Masuda, Takahiro [1 ]
Nozawa, Satoshi [1 ]
Dohjima, Taikoh [1 ]
Yamamoto, Takatoshi [1 ]
Nagano, Akihito [1 ]
Kawai, Gou [1 ]
Matsuhashi, Aya [1 ]
Saitoh, Mitsuru [1 ]
Takigami, Iori [1 ]
Okano, Yukio [2 ]
Shimizu, Katsuji [1 ]
机构：
[1] Gifu Univ, Grad Sch Med, Dept Orthopaed Surg, Gifu 5011194, Japan
[2] Gifu Univ, Grad Sch Med, Dept Mol Pathobiochem, Gifu 5011194, Japan
来源：
MOLECULAR CANCER RESEARCH | 2008年 / 6卷 / 12期
关键词：
D O I：
10.1158/1541-7786.MCR-08-0054
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
EWS-Fli1, a fusion gene resulting from the chromosomal translocation t(11;22, q24;q12), encodes a transcriptional activator, promotes cellular transformation, and is often found in Ewing sarcoma and primitive neuroectodermal tumor. The Aurora A and Aurora B kinases belong to a highly conserved family of serine/threonine protein kinases, are tightly regulated during the cell cycle, and are overexpressed in many carcinomas. Because the relationship between the Aurora A and/or Aurora B genes and the EWS-Fli1 fusion gene is unknown, we investigated the regulatory mechanism(s) by which Aurora kinases are controlled. Knockdown of EWS-Fli1 by small interfering RNA reduced mRNA levels not only of EWS-Fli1 but also of Aurora A and Aurora B. Luciferase assay using Aurora A and Aurora B promoters showed up-regulated activities compared with those of an empty vector. Experiments with deletion and point mutants showed positive regulatory Ets-binding sites located -84 and -71 by upstream of the transcription initiation sites in Aurora A and Aurora B, respectively. Moreover, chromatin immunoprecipitation assay revealed that EWS-Fli1 gene products interact with both the Aurora A and Aurora B promoters. These results strongly suggest that the mitotic kinases Aurora A and Aurora B are regulated by EWS-Fli1 fusion protein in Ewing sarcoma cells. (Mol Cancer Res 2008;6(12):1937-45)
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页码：1937 / 1945
页数：9
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