A role for survivin in radioresistance of pancreatic cancer cells.
Using gene-transduced pancreatic cancer cells, we examined whether survivin expression is directly involved in regulation of radiosensitivity. Ordinarily radiosensitive MIAPaCa-2 cells transduced with wild-type survivin gene (MS cells) proliferated more rapidly than cells transduced with control vector. MS cells were significantly less radiosensitive than control vector-transduced cells. Radiation-induced activity of caspase-3, but not caspase-7, was significantly inhibited in MS cells. On the other hand, transduction of a dominant-negative mutant survivin gene into radioresistant PANC-1 cells augmented radiosensitivity. Further, the radiation-induced increase in caspase-3 activity was enhanced, indicating that survivin function was truly inhibited. These results indicate that survivin expression directly down-regulates radiosensitivity.
D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000502:physiology*; D009363:Neoplasm Proteins; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000532:radiotherapy*; D011836:Radiation Tolerance; D000077022:Survivin; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured; D014965:X-Rays
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases