Centrosome Hypertrophy Induced by p53 Mutations Leads to Tumor Aneuploidy
Abstract
This research is designed to test the hypothesis that aneuploidy in some breast tumors is caused by centrosome abnormalities which are induced by alteration in p53 function. Specific mutations and expression alterations in p53 that are associated with breast cancer, aneuploidy, and centrosome abnormalities will be identified. To test whether or not a specific p53 mutation affects centrosome structure and function, normal mammary epithelial cells will be transfected to over-express mutant p53. These transfected cells will then be monitored for changes in ploidy and centrosome structure and function. First, tumor aneuploidy will be related to a spectrum of p53 mutations or expression alterations. Insights into the function of p53 will be gained by associating specific mutations with specific tumor phenotypes. Second, the effects of the mutations will be tested on primary cultures of normal human mammary epithelial cells. This portion of the research will actually test the hypothesis that some p53 mutations directly affect centrosome structure and function, resulting in aneuploidy. If specific pS3 mutations lead to aneuploidy by affecting centrosomes, then the possibility arises for development of new therapies that target centrosome function. To date we have shown that specific centrosome abnormalities are associated with abnormal mitoses in tumors and centrosome amplification has nearly 100% correlation with tumor aneuploidy. These results are currently being analyzed relative to p53 mutation status in the tumors.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2000
- Accession Number
- ADA389312
Entities
People
- Wilma Lingle