PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
Pharmacol Ther. Author manuscript; available in PMC May 1, 2008.
Published in final edited form as:
PMCID: PMC2039930
NIHMSID: NIHMS22413
Astrocyte Elevated Gene (AEG)-1: recent insights into a novel gene involved in tumor progression, metastasis and neurodegeneration
Luni Emdad,1,2 Devanand Sarkar,1 Zao-Zhong Su,1 Seok-Geun Lee,1 Dong-chul Kang,4 Jeffrey N. Bruce,2 David J. Volsky,3,5 and Paul B. Fisher1,2,3
1Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians and Surgeons, New York, NY
2Department of Neurosurgery, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians and Surgeons, New York, NY
3Department of Pathology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians and Surgeons, New York, NY
4Ilsong Institute of Life Science, Hallym University, Republic of Korea
5St. Luke's Roosevelt Medical Center, New York, NY
Corresponding Author: Dr. Paul B. Fisher Professor Departments of Pathology and Urology Columbia University Medical Center College of Physicians and Surgeons 630 West 168th Street New York, NY 10032 Tel: (212) 305-3642; -3441; Fax: (212) 305- 8177; E-mail pbf1/at/columbia.edu
Abstract
Tumor progression and metastasis are complex processes involving intricate interplay among multiple gene products. Astrocyte Elevated Gene (AEG)-1 was cloned as an HIV-1- and tumor necrosis factor α (TNF-α)-inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach. AEG-1 downregulates 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 NF-κB 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.
Keywords: AEG-1, Progression, Metastasis, Ha-ras oncogene, Glutamate excitotoxicity, AEG-1 promoter