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

Sangeeta Rojanala, Haiyong Han, Rubén M. Muñoz, Walden Browne, Raymond B. Nagle, Daniel D. Von Hoff, David J. Bearss

Molecular Cancer Therapeutics · 2004 · 78 citations · 21 references

DOIFull text

Open access

Concepts

Abstract

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.

References

21