The Effects of Deregulated Cyclin E Expression in Mitosis: A Role in Breast Tumorigenesis
Abstract
The objective of this study is to identify the mechanism through which deregulated expression of cyclin E leads to chromosome instability, first observed by Spruck et al. in rat and human cell lines. Cyclin E functions to regulate the timing of S phase entry and centrosome duplication in cells. Cyclin E overexpression is an indicator of poor prognosis is cancer patients; however the selective advantage gained by deregulating cyclin E has not yet been explained. We propose that in addition to delaying S phase, cyclin E deregulation also causes a delay in mitosis. Therefore, cyclin E may be interfering with mitotic division leading to chromosome instability and eventual tumorigenesis. In this first year of funding, I have accomplished my goals to observe and define the proposed mitotic delay using flow cytometry, immunofluorescence, and live cell microscopy. Cells were found delay in mitosis, specifically in prometaphase. In addition, we are now using biochemical assays to analyze expression of important mitotic regulators and identify a possible substrate of cyclin E/Cdk2 phosphorylation in mitosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2004
- Accession Number
- ADA425602
Entities
People
- Jamie M. Keck
Organizations
- Scripps Research