Association of MAD2 expression with mitotic checkpoint competence in hepatoma cells.
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.
Sze
Karen Man-Fong
KM
Department of Pathology, University of Hong Kong, Faculty of Medicine, Hong Kong, China.
Ching
Yick-Pang
YP
Jin
Dong-Yan
DY
Ng
Irene Oi-Lin
IO
D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D043171:Chromosomal Instability; D004252:DNA Mutational Analysis; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006367:HeLa Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D064246:Mad2 Proteins; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D012097:Repressor Proteins; D008941:Spindle Apparatus; D013997:Time Factors
D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012097:Repressor Proteins