Molecular Cancer Therapeutics
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Mol Cancer Ther. 2004;3:641-646
© 2004 American Association for Cancer Research

Identification of human polo-like kinase 1 as a potential therapeutic target in pancreatic cancer

Phillip J. Gray, Jr1, David J. Bearss2, Haiyong Han1, Raymond Nagle3, Ming-Sound Tsao4, Nicholas Dean5 and Daniel D. Von Hoff1

1 Arizona Cancer Center, 2 Department of Molecular and Cellular Biology, and 3 Department of Pathology, University of Arizona, Tucson, Arizona; 4 The Ontario Cancer Institute and the Department of Laboratory Medicine and Pathobiology, Toronto, Ontario, Canada; and 5 GeneTrove, Functional Genomics Division of Isis Pharmaceuticals Inc., Carlsbad, California

Requests for Reprints: Phillip J. Gray Jr., Arizona Cancer Center, Room 3916, 1515 North Campbell Avenue, Tucson, AZ 85724. Phone: (520) 626-8452; Fax: (520) 626-6898. E-mail: pjgray{at}email.arizona.edu

Pancreas cancer is the fourth leading cause of cancer-related death in adults in the United States. New molecular targets for diagnosis and therapy of this disease are desperately needed. In this study, we report on the mitotic serine-threonine kinase polo-like kinase 1 (Plk1) in pancreatic cancer. Plk1 mRNA was found to be overexpressed in 9 of 10 tested pancreatic cancer cell lines and in 4 of 4 tested human tumors. Immunohistochemical staining of a pancreatic tissue microarray showed that 26 of the 35 tumors taken directly from patients overexpressed Plk1. We also examined the effects of depleting Plk1 in pancreatic cancer cells by the use of antisense oligonucleotides. Antisense-treated pancreatic cancer cells showed cell cycle arrest in G2-M as well as a drastic reduction in proliferation rates. These data suggest that Plk1 is a potential therapeutic target in devising a treatment for patients with pancreatic cancer.

Key Words: Polo-like kinase • Molecular drug target • Cell cycle • Pancreatic cancer • Antisense • Oligonucleotides

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 6/24/03; revised 2/ 2/04; accepted 2/11/04.






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Copyright © 2004 by the American Association for Cancer Research.