Sphingolipid-Mediated Apoptosis and Tumor Suppression in Breast Carcinoma.
Abstract
Ceramide has emerged as an important intracellular regulator of cell growth and viability. In breast carcinoma cells, we find that tumor necrosis factor a (TNFa) causes prolonged and significant accumulation of ceramide, which precedes cell death. We have investigated the mechanism of ceramide formation and the mechanism of ceramide action, with specific emphasis on their interactions with proteases. Our studies lead us to define two phases of the apoptotic pathway: in the first, signaling phase, TNFa: causes activation of proteases which lead to the accumulation of ceramide. In the second, execution phase, ceramide causes the activation of downstream death proteases as well as activation of the retinoblastoma gene product. Addition of exogenous ceramides causes simultaneously cell cycle arrest and cell death. These studies are beginning to identify a growth suppressor pathway in breast carcinoma cells and the results are beginning to interrelate important components involved in the apoptotic response.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1996
- Accession Number
- ADB221779
Entities
People
- Yusuf A. Hannun
Organizations
- Duke University Hospital