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Astrocyte elevated gene-1: recent insights into a novel gene involved in tumor progression, metastasis and neurodegeneration.

Abstract：

:Tumor progression and metastasis are complex processes involving intricate interplay among multiple gene products. Astrocyte elevated gene (AEG)-1 was cloned as an human immunodeficiency virus (HIV)-1-inducible and tumor necrosis factor-alpha (TNF-alpha)-inducible transcript in primary human fetal astrocytes (PHFA) by a rapid subtraction hybridization approach. AEG-1 down-regulates the expression of the glutamate transporter EAAT2; thus, it is implicated in glutamate-induced excitotoxic damage to neurons as evident in HIV-associated neurodegeneration. Interestingly, AEG-1 expression is elevated in subsets of breast cancer, glioblastoma multiforme and melanoma cells, and AEG-1 cooperates with Ha-ras to augment the transformed phenotype of normal immortal cells. Moreover, AEG-1 is overexpressed in >95% of human malignant glioma samples when compared with normal human brain. Overexpression of AEG-1 increases and siRNA inhibition of AEG-1 decreases migration and invasion of human glioma cells, respectively. AEG-1 contains a lung-homing domain facilitating breast tumor metastasis to lungs. These findings indicate that AEG-1 might play a pivotal role in the pathogenesis, progression and metastasis of diverse cancers. Our recent observations indicate that AEG-1 exerts its effects by activating the nuclear factor kappa B (NF-kappaB) pathway and AEG-1 is a downstream target of Ha-ras and plays an important role in Ha-ras-mediated tumorigenesis. These provocative findings are intensifying interest in AEG-1 as a crucial regulator of tumor progression and metastasis and as a potential mediator of neurodegeneration. In this review, we discuss the cloning, structure and function(s) of AEG-1 and provide recent insights into the diverse actions and intriguing properties of this molecule.

journal_name

Pharmacol Ther

journal_title

Pharmacology & therapeutics

authors

Emdad L,Sarkar D,Su ZZ,Lee SG,Kang DC,Bruce JN,Volsky DJ,Fisher PB

doi

10.1016/j.pharmthera.2007.01.010

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

155-70

issue

eissn

0163-7258

issn

1879-016X

pii

S0163-7258(07)00033-2

journal_volume

114

pub_type

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Astrocyte elevated gene-1: recent insights into a novel gene involved in tumor progression, metastasis and neurodegeneration.