The mitotic serine threonine kinase, Aurora-2, is a potential target for drug development in human pancreatic cancer.
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.
Rojanala
Sangeeta
S
Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA.
Han
Haiyong
H
Muñoz
Rubén M
RM
Browne
Walden
W
Nagle
Raymond
R
Von Hoff
Daniel D
DD
Bearss
David J
DJ
D000970:Antineoplastic Agents / Q000494:pharmacology; D064127:Aurora Kinases; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D016195:G2 Phase / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*
D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases