A Novel Apoptosis Pathway that is Defective in Early Breast Cancer
Abstract
This grant was awarded to Dr. A. Thorburn but transferred to Dr. S. Cramer when Dr. Thorburn left Wake Forest University in Sept. 2004. The project examines a novel cell death pathway that is induced by the death domain of the adaptor protein FADDD (FADD-DD) FADD-DD-induced cell death occurs only in normal primary epithelial cells (from the breast or prostate) and can be inhibited when epithelial cells are immortalized e.g. by the expression of the telomerase catalytic subunit and the large and small T/t antigens from SV40 virus. The objectives of the project were to determine if T/t antigens cause resistance on their own and to determine how they do so. We found that Large T antigen was sufficient to confer selective resistance to this cell death pathway but that this resistance was not caused by the known activities of T antigen that are involved in immortalization including p53 inactivation or Rb inactivation. Moreover, we were able to expand our studies beyond that proposed in the grant and showed that the FADD-DD cell death pathway occurs in genetically-defined mouse epithelial cells and is selectively inactivated by spontaneous immortalization and that the cell death pathway involves both apoptosis and autophagy.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA436912
Entities
People
- Scott Cramer
Organizations
- Wake Forest University