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Clinical Cancer Research Vol. 10, 7304-7310, November 1, 2004
© 2004 American Association for Cancer Research

Molecular Oncology, Markers, Clinical Correlates

Overexpression of Aurora-A Contributes to Malignant Development of Human Esophageal Squamous Cell Carcinoma

Tong Tong2, Yali Zhong2, Jianping Kong2, Lijia Dong2, Yongmei Song2, Ming Fu2, Zhihua Liu2, Mingrong Wang2, Liping Guo3, Shixin Lu3, Ming Wu2 and Qimin Zhan2

2 State Key Laboratory of Molecular Oncology and 3 Department of Cancer Etiology, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China

Purpose: Aurora-A/STK15/BTAK, a centrosome-associated oncogenic protein, is implicated in the control of mitosis. Overexpression of Aurora-A has been shown to result in chromosomal aberration and genomic instability. Multiple lines of evidence indicate that Aurora-A induces cell malignant transformation. In the current study, we are interested in investigating the expression of Aurora-A in human esophageal squamous cell carcinoma (ESCC) and characterizing the association of Aurora-A with ESCCmalignant progression.

Experimental Design: Aurora-A protein expression was examined in 84 ESCC tissues and 81 paired normal adjacent tissues by either immunohistochemistry or Western blot analysis. In addition, a gene-knockdown small interfering RNA technique was used in ESCC cells to investigate whether Aurora-A contributes to the ability of a tumor to grow invasively.

Results: The amount of Aurora-A protein in ESCC was considerably higher than that in normal adjacent tissues. Overexpression of Aurora-A was observed in 57 of 84 (67.5%) ESCC samples. In contrast, <2% of normal adjacent tissue displayed high expression of Aurora-A. Interestingly, overexpression of Aurora-A seemed to correlate with the invasive malignancy of ESCC. Disruption of endogenous Aurora-A using small interfering RNA technique substantially suppressed cell migrating ability.

Conclusion: The findings presented in this report show that Aurora-A expression is elevated in human esophageal squamous cell carcinoma and is possibly associated with tumor invasion, indicating that overexpression of Aurora-A may contribute to ESCC occurrence and progression.




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Copyright © 2004 by the American Association for Cancer Research.