Mechanism of FADD-DN-Induced Apoptosis in Normal Breast Cells

Abstract

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. Because FADD is an essential component of receptor mediated apoptosis, a dominant-negative version (FADD-DN) is able to block apoptosis induced by death ligands in many cell lines. While studying FADD signaling, our laboratory made the surprising discovery that FADD-DN can induce apoptosis in normal breast epithelial cells. Because FADD-DN induces apoptosis in normal but not cancerous breast epithelial cells, we hypothesize that FADD-DN interacts with one or more proteins expressed in breast epithelia. Since breast tumor cells do not die in response to FADD- DN, the potential FADD-DN interacting partners are likely to be involved in carcinogenesis. Since defects in apoptotic pathways are a prerequisite to cancer, understanding the nature of these defects may bring about potential treatments. FADD-DN signaling presents a novel apoptotic pathway that is fundamental in normal breast epithelia, but not breast cancer cells. Components of this pathway may identify potential therapeutic targets that allow the reactivation of this apoptotic response in cancer cells.