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Journal of Biomedical Science

, Volume 11, Issue 6, pp 920–927 | Cite as

Association of MAD2 expression with mitotic checkpoint competence in hepatoma cells

  • Karen Man-Fong Sze
  • Yick-Pang Ching
  • Dong-Yan Jin
  • Irene Oi-Lin Ng
Original Paper

Abstract

Chromosomal instability (CIN) refers to high rates of chromosomal gains and losses and is a major cause of genomic instability of cells. It is thought that CIN caused by loss of mitotic checkpoint contributes to carcinogenesis. In this study, we evaluated the competence of mitotic checkpoint in hepatoma cells and investigated the cause of mitotic checkpoint defects. We found that 6 (54.5%) of the 11 hepatoma cell lines were defective in mitotic checkpoint control as monitored by mitotic indices and flow-cytometric analysis after treatment with microtubule toxins. Interestingly, all 6 hepatoma cell lines with defective mitotic checkpoint showed significant underexpression of mitotic arrest deficient 2 (MAD2), a key mitotic checkpoint protein. The level of MAD2 underexpression was significantly associated with defective mitotic checkpoint response (p<0.001). In addition, no mutations were found in the coding sequences of MAD2 in all 11 hepatoma cell lines. Our findings suggest that MAD2 deficiency may cause a mitotic checkpoint defect in hepatoma cells.

Key Words

MAD2 Cell cycle control Mitotic checkpoint Spindle assembly checkpoint Hepatocellular carcinoma Carcinogenesis Genome instability Chromosomal instability Microtubule toxin 

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Copyright information

© National Science Council 2004

Authors and Affiliations

  • Karen Man-Fong Sze
    • 2
  • Yick-Pang Ching
    • 2
    • 1
  • Dong-Yan Jin
    • 1
  • Irene Oi-Lin Ng
    • 2
  1. 1.Department of BiochemistryUniversity of Hong Kong, Faculty of MedicineHong KongChina
  2. 2.Department of PathologyUniversity of Hong Kong, Queen Mary Hospital PokfulamHong KongChina

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