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Mol Cancer Ther. 2004;3:451-457
© 2004 American Association for Cancer Research

The mitotic serine threonine kinase, Aurora-2, is a potential target for drug development in human pancreatic cancer

Sangeeta Rojanala1,2, Haiyong Han1,2, Rubén M. Muñoz1, Walden Browne1, Raymond Nagle1,3, Daniel D. Von Hoff1 and David J. Bearss1

1 Arizona Cancer Center and Departments of 2 Molecular and Cellular Biology and 3 Pathology, University of Arizona, Tucson, AZ

Requests for Reprints: Daniel D. Von Hoff, Arizona Cancer Center, University of Arizona, 1515 North Campbell Avenue, Tucson, AZ 85724. Phone: (520) 626-7925; Fax: (520) 626-6898. E-mail: dvonhoff{at}azcc.arizona.edu

Aurora-2 is a serine threonine kinase that associates with the centrosome. Overexpression or ectopic expression of Aurora-2 appears to alter centrosome number and function and has been implicated in a variety of human cancers. In this work, we demonstrate that Aurora-2 is both amplified and overexpressed in human pancreatic cancer cell lines, with a 2–5-fold increase in gene copy number and a 3–4-fold increase in protein levels compared with controls. Aurora-2 is also amplified and overexpressed in pancreatic cancers taken directly from patients. An immunohistochemistry of tissues taken directly from patients demonstrated an overexpression of Aurora-2 in 26 of 28 pancreatic cancers compared with 18 normal pancreas samples. Antisense nucleotides specifically targeted at Aurora-2 arrest the cell cycle in pancreatic cancer cells, indicating the potential of Aurora-2 as a therapeutic target in pancreatic cancer.


Grant support: NIH/National Cancer Institute (CA95031 and CA88310) and Arizona Cancer Center tissue culture shared service (grant P30CA023074).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 4/10/03; revised 1/20/04; accepted 1/27/04.







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Copyright © 2004 by the American Association for Cancer Research.