Astrocyte elevated gene-1 activates cell survival pathways through PI3K-Akt signaling

Oncogene. 2008 Feb 14;27(8):1114-21. doi: 10.1038/sj.onc.1210713. Epub 2007 Aug 20.


Astrocyte elevated gene-1 (AEG-1) displays oncogenic properties. Its expression is elevated in diverse neoplastic states and it cooperates with Ha-ras to promote cellular transformation. Overexpression of AEG-1 augments invasion and anchorage-independent growth of transformed cells, while AEG-1 siRNA inhibits Ha-ras-mediated colony formation, supporting a potential functional role in tumorigenesis. Additionally, oncogenic Ha-ras induces AEG-1 expression through the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. In the present study, we investigated whether AEG-1 could induce serum-independent cell growth, another property of oncogenes. Overexpression of AEG-1 inhibited serum starvation-induced apoptosis through activation of PI3K-Akt signaling, one of the effector pathways induced by activated Ras. AEG-1 also affected the phosphorylation state of Akt substrates that are implicated in apoptosis suppression, including glycogen synthase kinase 3beta, c-Myc, murine double minute 2, p53, p21/mda-6 and Bad. Additionally, AEG-1 blocked the activity of serum starvation-induced caspases. Taken together, these observations provide evidence that AEG-1 is an oncogene cooperating with Ha-ras as well as functioning as a downstream target gene of Ha-ras and may perform a central role in Ha-ras-mediated carcinogenesis. Activation of survival pathways may be one mechanism by which AEG-1 exerts its oncogenic properties.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / enzymology*
  • Cell Adhesion Molecules / physiology*
  • Cell Death / physiology
  • Cell Line, Transformed
  • Cell Survival / physiology
  • Gene Targeting
  • Genes, ras / physiology
  • Humans
  • Membrane Proteins / physiology*
  • Mice
  • Phosphatidylinositol 3-Kinases / physiology*
  • Proto-Oncogene Proteins c-akt / physiology*
  • RNA-Binding Proteins
  • Rats
  • Signal Transduction / physiology*
  • ras Proteins / physiology


  • Cell Adhesion Molecules
  • MTDH protein, human
  • Membrane Proteins
  • RNA-Binding Proteins
  • Proto-Oncogene Proteins c-akt
  • ras Proteins