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. In Year 1 of this project, we have generated several mutants of p55CDC which are defective in binding to Nad2 in the yeast two-hybrid system. In the current year (Year 2), we have placed these mutants under an inducible promoter and integrated in the genome of Hela cells. We have confirmed that some of these mutants are indeed defective in binding to Mad2 in vivo. We have also demonstrated that expression of the p55CDC mutants 1) abolishes a cell cycle arrest caused by a spindle poison, nocodazole and 2) produces aneuploid cells. These results indicate that we have succeeded in generating dominant p55CDC mutants which can abolish the function of the spindle checkpoint. 14. SUBJECT TERMS 15. NUMBER OF PAGES Breast Cancer, chromosome instability, spindle checkpoint, p55CDC 9
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA394079
Entities
People
- Tomohiro Matsumoto
Organizations
- Albert Einstein College of Medicine