Two molecular mechanisms of apoptosis resistance

摘要: Many cancer cells develop resistance to apoptosis. It is important understand how this phenotype develops, so that these cancers can be effectively treated. The results presented in dissertation describe two molecular mechanisms of apoptosis resistance. A mouse keratinocyte model system consisting the benign 308 parental cell line and malignantly progressed variants (6M90 6R90 cells) were used explore relationship between reactive oxygen species (ROS) Previous work showed elevated basal levels ROS 6M90 cells. shown here demonstrate increased UV-induced compared line. Pharmacological genetic approaches decrease steady-state malignant lines. This their sensitivity are implicated activation anti-apoptotic Akt kinase. had higher activated Akt. Modulation decreased These studies provide a mechanism explain chronically seen many tumors. Another by which tumor resist upregulate protein Bcl-2. putative response element (PPRE) for peroxisome proliferator nuclear receptor (PPAR) was found 3' UTR bd-2. Further experiments indicated y subtype PPAR bound PPRE could activate transcription. In transfected with PPARy, bd-2 mRNA