Akt deficiency impairs normal cell proliferation and suppresses oncogenesis in a p53-independent and mTORC1-dependent manner

Jennifer E. Skeen, Prashanth T. Bhaskar, Chia Chen Chen, William S. Chen, Xiao ding Peng, Veronique Nogueira, Annett Hahn-Windgassen, Hiroaki Kiyokawa, Nissim Hay*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

179 Scopus citations

Abstract

Akt contributes to tumorigenesis by inhibiting apoptosis. Here we establish that Akt is required for normal cell proliferation and susceptibility to oncogenesis independently of its antiapoptotic activity. Partial ablation of Akt activity by deleting Akt1 inhibits cell proliferation and oncogenesis. These effects are compounded by deleting both Akt1 and Akt2. In vivo, Akt1 null mice are resistant to MMTV-v-H-Ras-induced tumors and to skin carcinogenesis. Thus, partial ablation of Akt activity is sufficient to suppress tumorigenesis in vitro and in vivo. The effect of Akt deficiency on cell proliferation and oncogenesis is p53 independent but mTORC1 dependent. Surprisingly, upon mTORC1 hyperactivation, the reduction in Akt activity does not impair cell proliferation and susceptibility to oncogenic transformation; thus, Akt may mediate these processes exclusively via mTORC1.

Original languageEnglish (US)
Pages (from-to)269-280
Number of pages12
JournalCancer Cell
Volume10
Issue number4
DOIs
StatePublished - Oct 2006

Keywords

  • CELLCYCLE
  • RNA
  • SIGNALING

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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