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.

[1]  Jian Kuang,et al.  Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation , 1998, Nature Genetics.

[2]  Feng Jiang,et al.  Amplification/overexpression of a mitotic kinase gene in human bladder cancer. , 2002, Journal of the National Cancer Institute.

[3]  D. V. Von Hoff,et al.  Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  D. Botstein,et al.  Isolation and characterization of chromosome-gain and increase-in-ploidy mutants in yeast. , 1993, Genetics.

[5]  C. Prigent,et al.  Aurora/Ipl1p-related kinases, a new oncogenic family of mitotic serine-threonine kinases. , 1999, Journal of cell science.

[6]  Domenico Coppola,et al.  Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[7]  J. Bischoff,et al.  The Aurora/Ipl1p kinase family: regulators of chromosome segregation and cytokinesis. , 1999, Trends in cell biology.

[8]  S. Kotani,et al.  Cell Cycle-dependent Expression and Spindle Pole Localization of a Novel Human Protein Kinase, Aik, Related to Aurora of Drosophila and Yeast Ipl1* , 1997, The Journal of Biological Chemistry.

[9]  Masafumi Nakamura,et al.  Centrosome abnormalities in pancreatic ductal carcinoma. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[10]  C. McNeil Herceptin raises its sights beyond advanced breast cancer. , 1998, Journal of the National Cancer Institute.

[11]  S. Sen,et al.  A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines , 1997, Oncogene.

[12]  Alicia Samuels,et al.  Cancer Statistics, 2003 , 2003, CA: a cancer journal for clinicians.

[13]  Y. Nakamura,et al.  Tumour-amplified kinase BTAK is amplified and overexpressed in gastric cancers with possible involvement in aneuploid formation , 2001, British Journal of Cancer.

[14]  H Knecht,et al.  Centrosome defects and genetic instability in malignant tumors. , 1998, Cancer research.

[15]  Haiyong Han,et al.  Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarray. , 2002, Cancer research.

[16]  Clarence S. M. Chan,et al.  A Novel Mammalian, Mitotic Spindle–associated Kinase Is Related to Yeast and Fly Chromosome Segregation Regulators , 1997, The Journal of cell biology.

[17]  L. Norton,et al.  Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. , 1998, Cancer research.

[18]  D. Glover,et al.  Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles , 1995, Cell.

[19]  H. Mori,et al.  Centrosomal kinase AIK1 is overexpressed in invasive ductal carcinoma of the breast. , 1999, Cancer research.

[20]  P. Meltzer,et al.  Frequent amplification of chromosomal region 20q12-q13 in ovarian cancer. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[21]  J. Schumacher,et al.  A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos. , 1998, Development.

[22]  Brian Schryver,et al.  A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers , 1998, The EMBO journal.

[23]  G. Clark,et al.  Amplification of c-erbB-2 and aggressive human breast tumors? , 1988, Science.

[24]  S. Doxsey The centrosome — a tiny organelle with big potential , 1998, Nature Genetics.