Akt1 deletion prevents lung tumorigenesis by mutant K-ras

摘要: K-ras mutations are associated with smoking-induced lung cancer and poor clinical outcomes. In mice, sufficient to induce tumors, which require phosphoinoside-3-kinase (PI3K) further downstream, mammalian target of rapamycin (mTOR) activation. However, the roles individual Akt isoforms that link PI3K mTOR unknown. Here, we show deletion Akt1 but not Akt2 or Akt3 prevents tumorigenesis in a tobacco carcinogen-induced model genetic model. prevented tumor initiation as well progression, coincident decreased signaling tissues. contrast, increased multiplicity carcinogen size Fibroblasts lacking resistant transformation by mutant stimulation epidermal growth factor. Human cells diminished levels fail grow vivo. These data suggest is primary isoform activated may oppose progression. Given inhibitors development therapeutics selective, these studies support specific targeting mitigate effects cancer.