Mechanism of FADD-DN-Induced Apoptosis in Normal Breast Cells
Abstract
Normal cells undergo apoptosis in response to inappropriate growth signals or the lack of overt survival signals. Tumor cells possess defects in apoptosis regulatory pathways and do not undergo apoptosis in these situations. There are two modes of apoptosis - an intrinsic pathway initiated by stress such as DNA damage and an extrinsic pathway resulting from activation of death receptors. Binding of ligand to a death receptor such as Fas, TNFRl or TRAIL receptors 1 and 2 leads to activation of that receptor. This results in the recruitment of a cytoplasmic adaptor protein FADD to the receptor complex and activation of caspase-8. Because FADD is an essential component of receptor mediated apoptosis, a dominant-negative version (FADD-DN) is able to block both Fas and TNF induced apoptosis in many cell lines. However, experiments in our lab indicate that FADD-DN can kill normal human breast epithelial cells but not breast tumor cells. Since the only known role of FADD is an adaptor molecule, this suggests that FADD-DN interacts with one or more proteins expressed in breast epithelia. Because breast tumor cells do not die in response to FADD-DN, the potential FADD-DN interacting partners are likely to be involved in carcinogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2003
- Accession Number
- ADA417051
Entities
People
- Lance R. Thomas
Organizations
- Wake Forest University