Molecular Basis of Genomic Instability in Breast Cancer: Regulation of the Centrosome Duplication Cycle
Abstract
This award (DAMD 17-02-1-0344) supports the study of genomic instability in breast cancer cells from the June 1st, 2002 to the May 31st, 2005. The hypothesis that centrosome abnormality may induce genomic instability was studied focusing on a mitotic kinases: Aurora kinases, which overexpression induces centrosome amplification, cellular transformation and aneuploidy. Two experimental approaches were taken: one was a genetic screen looking for its protein partners using two-hybrid screen performed in S. cerevisiae (annual report 2003 and 2005). Aurora-A interacting protein NM23-H1 and astrin were identified and characterized biochemically and geneticly. The second proteomic approach was taken to purify and identify the Aurora-A protein complex (annual report 2004 and 2005). p160ROCK were characterized as an Aurora-A kinase substrate and a genetic suppressor, which the interaction promotes the genomic instability in cancer cell lines. The results are published in Nuclei Acid Research (2002), PNAS (2004), and submitted (see key research accomplishment1-3), as well as reported in various scientific meetings (reportable outcomes 1-5).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2005
- Accession Number
- ADA444650
Entities
People
- Gregory Hannon
- Jianbin Du
Organizations
- Cold Spring Harbor Laboratory