Carcinogenesis Advance Access first published online on June 15, 2006
This version published online on July 13, 2006
Carcinogenesis, doi:10.1093/carcin/bgl100
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1 Human Genetics and Genomics Division, Indian Institute of Chemical Biology, Kolkata-700 032, India
* To whom correspondence should be addressed. 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 (SCC) 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 oral SCC cell lines. We also reconstituted the chromosomal instability phenotype in a chromosomally stable oral SCC 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.
Received September 21, 2005
Revised May 26, 2006
Accepted May 27, 2006
CANCER BIOLOGY
Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer
Gourish Mondal 1,
Shiladitya Sengupta 1,
Chinmoy K. Panda 2,
Susanne M. Gollin 3,
William S. Saunders 4,
and
Susanta Roychoudhury 1 *
2 Department of Oncogene Regulation, Chittaranjan National Cancer Institute, Kolkata-700 026, India
3 Department of Human Genetics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA15261, USA
4 Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
Susanta Roychoudhury, E-mail: susanta{at}iicb.res.in; susanta_rc@yahoo.co.in
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