Overexpression of the oncogenic kinase Pim-1 leads to genomic instability.
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.
Roh
Meejeon
M
Department of Pathology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama 35294-0007, USA.
Gary
Bernard
B
Song
Chisu
C
Said-Al-Naief
Nasser
N
Tousson
Albert
A
Kraft
Andrew
A
Eltoum
Isam-Eldin
IE
Abdulkadir
Sarki A
SA
D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D020090:Chromosome Segregation; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008297:Male; D008938:Mitosis / Q000235:genetics; D011123:Polyploidy; D011467:Prostate / Q000201:enzymology / Q000502:physiology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051573:Proto-Oncogene Proteins c-pim-1; D008941:Spindle Apparatus / Q000235:genetics
D011518:Proto-Oncogene Proteins; C496634:PIM1 protein, human; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1