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

Mol Cancer Ther. 2004 Apr;3(4):451-7.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Aurora Kinases
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cell Line, Tumor
  • G2 Phase / drug effects
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / pharmacology
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Oligonucleotides, Antisense
  • Aurora Kinases
  • Protein Serine-Threonine Kinases