Significance of MAD2 expression to mitotic checkpoint control in ovarian cancer cells - PubMed (original) (raw)
. 2002 Mar 15;62(6):1662-8.
Affiliations
- PMID: 11912137
Significance of MAD2 expression to mitotic checkpoint control in ovarian cancer cells
Xianghong Wang et al. Cancer Res. 2002.
Erratum in
- Cancer Res. 2005 Mar 1;65(5):2045
- Cancer Res. 2012 Apr 1;72(7):1905
- Correction: Significance of MAD2 Expression to Mitotic Checkpoint Control in Ovarian Cancer Cells.
[No authors listed] [No authors listed] Cancer Res. 2018 Aug 15;78(16):4800. doi: 10.1158/0008-5472.CAN-18-1290. Cancer Res. 2018. PMID: 30111651 No abstract available.
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 molecular basis of CIN in ovarian carcinoma and has implications for effective use of checkpoint-targeting drugs.
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