Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells
Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells
复制标题
DOI：
10.1158/1535-7163.mct-06-0560
复制
发表时间：
2007-01-01
影响因子：
5.7
通讯作者：
Fesik, Stephen W.
中科院分区：
文献类型：
--
作者：
Sarthy, Aparna V.;Morgan-Lappe, Susan E.;Fesik, Stephen W.
To identify cancer-specific targets, we have conducted a synthetic lethal screen using a small interfering RNA (siRNA) library targeting similar to 4,000 individual genes for enhanced killing in the DLD-1 colon carcinoma cell line that expresses an activated copy of the K-Ras oncogene. We found that siRNAs targeting baculoviral inhibitor of apoptosis repeat-containing 5 (survivin) significantly reduced the survival of activated K-Ras-transformed cells compared with its normal isogenic counterpart in which the mutant K-Ras gene had been disrupted (DKS-8). In addition, survivin siRNA induced a transient G(2)-M arrest and marked polyploidy that was associated with increased caspase-3 activation in the activated K-Ras cells. These results indicate that tumors expressing the activated K-Ras oncogene may be particularly sensitive to inhibitors of the survivin protein.
