PMID: 11912137Mar 26, 2002Paper

Significance of MAD2 expression to mitotic checkpoint control in ovarian cancer cells

Cancer Research
Xianghong WangSai W Tsao

Abstract

Chromosome instability is a commonly observed feature in ovarian carcinoma. Mitotic checkpoint controls are thought to be essential for accurate chromosomal segregation, and MAD2 is a key component of this checkpoint. In this study, we investigated the competence of the mitotic checkpoint and its relationship to the expression of MAD2 protein in seven ovarian cancer cell lines. We found that a significant number (43%, three of seven cell lines) of the tested ovarian cancer cells failed to arrest in the G(2)-M phase of the cell cycle in response to microtubule disruption. This loss of mitotic checkpoint control was associated with reduced expression of the MAD2 protein. To additionally understand the significance of the MAD2 to mitotic checkpoint control, we established an inducible expression system in which MAD2 was induced by the addition of ponasterone A. Notably, the induced expression of MAD2 in two checkpoint-defective ovarian cancer cell lines led to the restoration of mitotic checkpoint response to spindle-disrupting agents. Taken together, our findings suggest that the steady-state amount of MAD2 inside cells may represent a molecular switch for mitotic checkpoint control. This provides a novel insight into the molecul...Continue Reading

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.