Hypoxia as a Driving Force for Genetic Instability During Breast Tumorigenesis
Abstract
The overall hypothesis that drives this project is that persistent replication stress generates mutational events in breast epithelial cells that fuel breast cancer (BCa) progression. Our model predicts that a major source of replicative stress in BCa is hypoxia, which stalls active replication forks, and selects for cells that have bypassed the this S-phase checkpoint due to mutations in the ATR-hchkl pathway. The specific aims of this project are: (1) to define the role of the ATR checkpoint pathway in hypoxia-induced cytostasis, and (2) to determine whether defects in this checkpoint pathway promotes BCa progression, and confers sensitivity to killing by certain anticancer agents.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2004
- Accession Number
- ADA435033
Entities
People
- Robert T. Abraham
Organizations
- Sanford Burnham Prebys Medical Discovery Institute