Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer

Gourish Mondal, Shiladitya Sengupta, Chinmoy K Panda, Susanne M Gollin, William S Saunders, Susanta Roychoudhury

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Defects in the spindle assembly checkpoint are thought to be responsible for an increased rate of aneuploidization during tumorigenesis. Despite a plethora of information on the correlation between BUB-MAD gene expression levels and defects in the spindle checkpoint, very little is known about alteration of another important spindle checkpoint protein, Cdc20, in human cancer and its role in tumor aneuploidy. We observed overexpression of CDC20 in several oral squamous cell carcinoma (OSCC) cell lines and primary head and neck tumors and provide evidence that such overexpression of CDC20 is associated with premature anaphase promotion, resulting in mitotic abnormalities in OSCC cell lines. We also reconstituted the chromosomal instability phenotype in a chromosomally stable OSCC cell line by overexpressing CDC20. Thus, abnormalities in the cellular level of Cdc20 may deregulate the timing of anaphase promoting complex (APC/C) in promoting premature anaphase, which often results in aneuploidy in the tumor cells.

Original languageEnglish (US)
Pages (from-to)81-92
Number of pages12
JournalCarcinogenesis
Volume28
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • Anaphase-Promoting Complex-Cyclosome
  • Aneuploidy
  • Carcinoma, Squamous Cell
  • Cdc20 Proteins
  • Cell Cycle
  • Cell Cycle Proteins
  • Cell Proliferation
  • Chromosomal Instability
  • Cyclin B
  • Cyclin B1
  • Fluorescent Antibody Technique
  • Head and Neck Neoplasms
  • Humans
  • Immunoblotting
  • Mitosis
  • Mitotic Index
  • Mouth Neoplasms
  • Phenotype
  • Spindle Apparatus
  • Transfection
  • Tumor Cells, Cultured
  • Ubiquitin-Protein Ligase Complexes

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