Hypoxia as a Driving Force for Generic Instability During Breast Tumorigenesis
Abstract
The overall hypothesis that drives this project is that the involvement of particular tumor suppressor genes, such as BRCA1 and BRCA2, in familial breast cancer (BCa) provides important clues regarding the etiology of the far more common, sporadic form of this disease. These two breast cancer susceptibility genes play central roles in genome surveillance during the process of DNA replication in proliferating cells. We hypothesize that BCa progression is fueled by the accumulation of cancer-promoting mutations due to errors in genome duplication during S phase. According to our model, hypoxia in developing tumors leads to cell growth arrest during S-phase, and selects for cells that have bypassed the this S-phase checkpoint due to mutations in the ATR-hChk1 pathway. The specific aims of this project are: 91) to define the role of the ART 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, 2003
- Accession Number
- ADA421845
Entities
People
- Robert T. Abraham
Organizations
- Sanford Burnham Prebys Medical Discovery Institute