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PMID:17704808

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Citation

Lee, SG, Su, ZZ, Emdad, L, Sarkar, D, Franke, TF and Fisher, PB (2008) Astrocyte elevated gene-1 activates cell survival pathways through PI3K-Akt signaling. Oncogene 27:1114-21

Abstract

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.

Links

PubMed Online version:10.1038/sj.onc.1210713

Keywords

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; Rats; Signal Transduction/physiology; ras Proteins/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:LYRIC

involved_in

GO:0043066: negative regulation of apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:LYRIC

involved_in

GO:0051897: positive regulation of protein kinase B signaling

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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