Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells.

Sarthy AV, Morgan-Lappe SE, Zakula D, Vernetti L, Schurdak M, Packer JC, Anderson MG, Shirasawa S, Sasazuki T, Fesik SW
Mol Cancer Ther. 2007 6 (1): 269-76

PMID: 17237286 · DOI:10.1158/1535-7163.MCT-06-0560

To identify cancer-specific targets, we have conducted a synthetic lethal screen using a small interfering RNA (siRNA) library targeting approximately 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.

MeSH Terms (18)

Alleles Apoptosis Cell Death Cell Survival Cell Transformation, Neoplastic Clone Cells G2 Phase Genes, Neoplasm Genes, ras Humans Inhibitor of Apoptosis Proteins Microtubule-Associated Proteins Mitosis Mutant Proteins Neoplasm Proteins Polyploidy RNA, Small Interfering Survivin

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