A Novel Apoptosis Pathway That is Defective in Early Breast Cancer
Annual rept. 1 Apr 2002-31 Mar 2003
WAKE FOREST UNIV WINSTON-SALEM NC SCHOOL OF MEDICINE
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This project studies a novel apoptosis pathway that is induced by the death domain of the adapter protein FADD FADD-DD. This pathway induces apoptosis in normal breast epithelial cells but not in breast cancer cells and the project is to determine why cancer cells are resistant to this apoptosis. In this report, we show that resistance to this apoptosis pathway occurs in response to the oncogene sv4O Large T antigen acting alone. Furthermore, we show that this defect arises at the earliest stages of breast cancer development thus identifying the FADD-DD pathway as a very early, perhaps the first, apoptotic defect in breast cancer development. We also demonstrate that the apoptosis pathway can occur in mouse epithelial cells. Future studies in this project as described in the approved statement of work will determine how this resistance arises.
- Medicine and Medical Research