BARC: A Novel Apoptosis Regulator
Abstract
Breast cancers arise due to an imbalance in cell production relative to cell turnover, resulting in a net accumulation of abnormal cells. Cell turnover is normally achieved through programmed cell death, also known as apoptosis. Effects in apoptosis occur in breast cancers and other types of malignancies, making tumor cells difficult to kill by chemotherapy, hormonal therapy, and radiation. Restoring function of cell death pathways is a strategy for improving treatment of breast cancer. This project focused on two anti-apoptotic proteins discovered by our laboratory, BI-1 and BI-2 (also known as BAR). The findings provided insights into the mechanism by which these proteins protect cancer cells from specific types of death stimuli. Proof of concept experiments demonstrated that interfering with expression or function of BI-2 (BAR) restores sensitivity of tumor cells to the killing mechanisms employed by immune cells, such as activators of the TNF-family receptor member Fas (CD95). We also observed that BI-1 protects cells from cell death induced by ER stress reagents, and regulates homeostasis of Ca(2+) in the ER. We found that regulating ER Ca(2+) homeostasis is a common way for anti-apoptotic proteins such as Bcl-2 and Bcl-xL to protect cells. Green tea compounds that inhibit Bcl-2 can restore normal ER calcium regulation. These findings provide new insights into cell death regulation in breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2004
- Accession Number
- ADA436913
Entities
People
- Can Jin
- Han J. Chae
- Hong Zhang
- John C. Reed
Organizations
- Sanford Burnham Prebys Medical Discovery Institute