Co-Operation Between FADD and Bin1 in Prostate Cancer Apoptosis
Abstract
Evasion of apoptosis is a hallmark of cancer (Hanahan and Weinberg, 2000). Consequently, it is sometimes thought that cancer cells are generally resistant to apoptosis while normal cells are sensitive. In fact cancer cells are actually closer to their apoptotic threshold than their normal counterparts and therefore often undergo apoptosis more easily in response to diverse apoptotic stimuli (Evan and Vousden, 2001). This apoptosis sensitization occurs because growth promoting oncogenic events such as Myc expressipn raise the levels of caspases and other apoptotic proteins or make it easier to activate these molecules and thus reduce the threshold at which apoptosis is activated. However, it is not clear ff this is the only apoptotic barrier that cancer cells must overcome as they become transformed. Are there also specific apopt6sis pathways that inhibit cancer development and are active in normal cells and specifically inactivated during tumor development? We hypothesized that such a pathway would have the unusual characteristic of working in normal cells but not in cancer cells. Furthermore unlike most apoptotic stimuli, which usually work better in cancer cells than their normal counterparts because they are closer to their apoptotic threshold, signaling proteins and physiological stimuli that activate this kind of pathway should induce specific apoptosis responses in normal cells that should be selectively inhibited in cancer cells without affecting responsiveness to other apoptotic stimuli. The apoptosis pathway we study that is induced by FADD-DD has these characteristics because it works in normal epithelial cells but does not work in immortalized epithelial cells. Tumor cells are not normally sensitive to FADD-DD-induced apoptosis, however, we discovered that a prostate cell line (LNCaP) could become sensitive if we express the Bini tumor suppressor. This project is designed to further investigate this response.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA427175
Entities
People
- Andrew M. Thorburn
Organizations
- Wake Forest University