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Title: The effects of knockdown of wild-type survivin, survivin-2B or survivin-delta3 on the radiosensitization in a soft tissue sarcoma cells in vitro under different oxygen conditions. Author: Kappler M, Rot S, Taubert H, Greither T, Bartel F, Dellas K, Hänsgen G, Trott KR, Bache M. Journal: Cancer Gene Ther; 2007 Dec; 14(12):994-1001. PubMed ID: 17885676. Abstract: The inhibitor of apoptosis wild-type survivin is a multifunctional protein that suppresses apoptosis and regulates cell cycle progression. An association between wild-type survivin expression and radiosensitivity has been described in different tumor cells. The effects of siRNA-induced knockdown of wild-type survivin and survivin-splice variants survivin-2B and survivin-Delta3 were investigated under normoxic and hypoxic conditions in the human sarcoma cell line US 8-93 (mutant p53). Inhibition of the survivin isoforms by siRNA resulted in a decrease of target mRNA down to 14-70% compared to cells treated with control siRNA independent of the oxygen level. The mRNA expression of survivin isoforms was decreased by the factor of 1-12 when the cells were cultivated under hypoxic conditions. Moreover, the knockdown of wild-type survivin reduced colony formation independent of oxygen concentration down to 70% and induced formation of polyploid cells. Less reduction of plating efficiency was observed after specific knockdown of survivin-2B and survivin-Delta3 under hypoxic or normoxic conditions. A knockdown of wild-type survivin, survivin-Delta3 and survivin-2B isoforms in combination with irradiation caused no radiosensitization in cell line US 8-93, neither under hypoxic nor under normoxic conditions tested in the colony-forming assay. However, knockdown of wild-type survivin caused radiosensitization in the megacolony assay.[Abstract] [Full Text] [Related] [New Search]