Description:
<jats:title>ABSTRACT</jats:title>
<jats:p>
Reovirus T3D is an oncolytic agent that preferentially targets tumor cells expressing an activated
<jats:italic>Ras</jats:italic>
oncogene. Ras signaling interferes with the cellular stress response that inhibits translation of reovirus RNAs. Murine C26 colorectal carcinoma cells express a mutant Kras
<jats:sup>D12</jats:sup>
gene. Reovirus T3D efficiently kills C26 cells, but not C26 cells in which the Kras
<jats:sup>D12</jats:sup>
mRNA is stably repressed by expression of Kras
<jats:sup>D12</jats:sup>
-directed short-hairpin RNAs. Surprisingly, neither reovirus T3D protein synthesis nor T3D virus yields were suppressed by deletion of Kras
<jats:sup>D12</jats:sup>
. Rather, reovirus-induced tumor cell apoptosis was completely abrogated as a result of
<jats:italic>Kras</jats:italic>
knockdown. We conclude that sensitization of C26 tumor cells to reovirus-induced apoptosis underlies the Ras dependency of reovirus T3D oncolysis.
</jats:p>