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)

引用

页码：1937 / 1945

页数：9

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