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 chromosome stability. The authors 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. This 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 feedback manner by activating more Caspases. Overexpression of the C-terminal cleavage products results in apoptosis in MCF-7 breast cancer cells. Given the role of human Rad21 (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. Following this 9-page report are four appendixes: statement/timeline of work accomplished, bibliography of publications and meeting abstracts, a list of participating personnel, and a reprint of "Linking Sister Chromatid Cohesion and Apoptosis: Role of Rad21," by Debananda Pati, Nenggang Zhang, and Sharon E. Plon (Molecular and Cellular Biology, v22 n23, p8267-8277, Dec 2002).
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2005
- Accession Number
- ADA444254
Entities
People
- Debananda Pati
Organizations
- Baylor College of Medicine