Akt1 deletion prevents lung tumorigenesis by mutant K-ras.

ABSTRACT: K-ras mutations are associated with smoking-induced lung cancer and poor clinical outcomes. In mice, K-ras mutations are sufficient to induce lung tumors, which require phosphoinoside-3-kinase (PI3K) and further downstream, mammalian target of rapamycin (mTOR) activation. However, the roles of individual Akt isoforms that link PI3K and mTOR are unknown. Here, we show that deletion of Akt1 but not Akt2 or Akt3 prevents lung tumorigenesis in a tobacco carcinogen-induced model and a genetic model. Akt1 deletion prevented tumor initiation as well as tumor progression, coincident with decreased Akt signaling in tumor tissues. In contrast, deletion of Akt3 increased tumor multiplicity in the carcinogen model and increased tumor size in the genetic model. Fibroblasts lacking Akt1 are resistant to

SUBMITTER: Hollander MC 

PROVIDER: S-EPMC4133779 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature