Comparison of the genetic extinction of NRAS to pharmacological MEK inhibition in an inducible mouse model of melanoma

ABSTRACT: Since direct pharmacological inhibition of RAS has thus far been unsuccessful, we explored system biology approaches to identify synergistic drug combination(s) that can mimic direct RAS inhibition. Leveraging an inducible mouse model of NRAS-mutant melanoma, we compare pharmacological MEK inhibition to complete NRAS-Q61K extinction in vivo. NRAS-Q61K extinction leads to a complete and durable tumor regression by enhancing both apoptosis and cell cycle arrest. By contrast, MEK inhibition only produces tumor stasis at best and we find that it robustly activates apoptosis but does not significantly impede proliferation. We used microarrays to determine which transcripts were affected by NRAS-Q61K extinction but insufficiently by MEK inhibition. We selected a single comparative timepoint, 4

ORGANISM(S): Mus musculus

SUBMITTER: Lawrence Kwong 

PROVIDER: E-GEOD-39984 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress