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

• Published in: Carcinogenesis (New York) Vol. 28; no. 1; pp. 81 - 92
• Main Authors: Mondal, Gourish, Sengupta, Shiladitya, Panda, Chinmoy K., Gollin, Susanne M., Saunders, William S., Roychoudhury, Susanta
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.01.2007; Oxford Publishing Limited (England)
• Subjects: Anaphase-Promoting Complex-Cyclosome; Aneuploidy; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Cdc20 Proteins; Cell Cycle; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell Proliferation; Chromosomal Instability; Cyclin B - metabolism; Cyclin B1; Fluorescent Antibody Technique; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Humans; Immunoblotting; Medical sciences; Mitosis; Mitotic Index; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Otorhinolaryngology. Stomatology; Phenotype; Spindle Apparatus; Transfection; Tumor Cells, Cultured; Tumors; Ubiquitin-Protein Ligase Complexes; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Oral cavity; Oral cancer; Stomatology; Gene overexpression; Activity; Oral cavity disease; Malignant tumor; Mechanism of action; Control point
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgl100

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.