Role of the Spindle Checkpoint in Preventing Breast Cancer
Abstract
Abnormal chromosome number is a phenotype characteristic for most of the cancer cells. Thus, it may be a direct cause of human cancer including breast cancer. In this research project, we aim to test this hypothesis by abrogating the spindle checkpoint that is a major surveillance mechanism responsible for maintenance of the normal chromosome number. p55cDc serves as a target of the checkpoint. If it is unable to bind to a spindle checkpoint protein, Mad2, it abrogates the checkpoint in a dominant manner. We have generated several p55CDC mutants that have lost the ability to interact with Mad2, but otherwise normal. These mutants, when expressed in Hela cells, abrogate the spindle checkpoint expectedly. In BJ cell line, they are however toxic and we failed to establish an experimental system to test if a loss of the checkpoint causes chromosome instability and neoplasmic transformation. As an alternative strategy, we propose overexpression of Cmt2. Cmt2 is a novel Mad2-binding protein we have identified recently. Our characterization indicates that Cmt2 may directly interact with the p55CDC-Mad2 complex and promote dissociation of the complex. In the normal cell cycle, it may play a role as a silencer of the checkpoint.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA407299
Entities
People
- Tomohiro Matsumoto
Organizations
- Albert Einstein College of Medicine