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1 Department of Pathology,
2 Division of Hematology and Oncology, and
3 High Resolution Imaging Facility and Department of Cell Biology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, and
4 Division of Medical Oncology, University of Colorado Health Science Center, Denver, Colorado
Aneuploidy and chromosomal aberrations are hallmarks of most human epithelial malignancies. Here we show that overexpression of the oncogenic kinase Pim-1 in human prostate epithelial cells induces genomic instability by subverting the mitotic spindle checkpoint. Cells overexpressing Pim-1 have a defect in the mitotic spindle checkpoint, abnormal mitotic spindles, centrosome amplification, and chromosome missegregation. Polyploidy and aneuploidy ensue due to a delay in completing cytokinesis. These results define a novel role for elevated Pim-1 expression in promoting genomic instability in human prostate tumors.
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