Linking Sister Chromatid Cohesion to Apoptosis and Aneuploidy in the Development of Breast Cancer
Abstract
The purpose of this project is to identify effector molecules that act as a link between cell proliferation, cell survival and chromosomes stability. We have hypothesized that chromosomal segregation and apoptotic pathways are linked and have a role in breast cancer. Rad21 is one of the major cohesin subunits that holds sister chromatids together until anaphase, when proteolytic cleavage by separase allows chromosomal separation. Our study demonstrates that in contrast to described functions of Rad21, in chromosome segregation and DNA repair, cleavage of the cohesion protein and translocation of the C-terminal cleavage product to the cytoplasm are early events in the apoptotic pathway that amplify the apoptotic signal in a positive feed back manner by activating more Caspases. Overexpression of the 64 kDa cleavage product results in apoptosis in MCF-7 breast cancer cells. Given the role of hRad21 in chromosome cohesion, the cleaved C-terminal product and its translocation to the cytoplasm may act as a nuclear signal for apoptosis. Furthermore, hRad21 is differentially expressed in human breast tumors and in breast cancer derived cell lines in comparison to normal breast epithelial cells. Future studies will identify the protease that cleaves Rad21 and evaluate hRad21 as a prognostic marker for breast cancer development.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA427750
Entities
People
- Debananda Pati
Organizations
- Baylor College of Medicine