The Role of G2/M Checkpoint Controls in Cytotoxic Treatment of Breast Cancer.
Abstract
The objective of the work is to provide a detailed understanding of the molecular mechanism by which G2/M regulation is achieved in human cells. In particular we are focusing on how initiation of M-phase is delayed in cells that have been treated with agents that induce DNA damage or that prevent synthesis of DNA. By providing a more detailed explanation of how cytotoxic therapies brings about cell death we hope to provide clinicians with better tools for the treatment of breast cancer. Human cell-lines that over-express non- phosphorylatable mutants of CDC2 were used to establish the importance of inhibitory phosphorylation of CDC2 in checkpoint control in human cells. We have demonstrated that the activity of Cdc25, the phosphatase that activate Cdc2, is decreased in response to damaged DNA. We have identified a human homolgue of the checkpoint kinase, hChkl, that phosphorylates and inactivates Cdc25 in vitro. Experiments are underway to determine the exact molecular details by which DNA damage leads to inactivation of Cdc25.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1997
- Accession Number
- ADA340581
Entities
People
- Clare H. Mcgowan
Organizations
- Scripps Research