Astrocyte elevated gene-1: recent insights into a novel gene involved in tumor progression, metastasis and neurodegeneration.
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.
Emdad
Luni
L
Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians and Surgeons, New York, NY 10032, USA.
Sarkar
Devanand
D
Su
Zao-Zhong
ZZ
Lee
Seok-Geun
SG
Kang
Dong-Chul
DC
Bruce
Jeffrey N
JN
Volsky
David J
DJ
Fisher
Paul B
PB
D001932:Brain Neoplasms / Q000235:genetics / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D018450:Disease Progression; D005786:Gene Expression Regulation; D015658:HIV Infections / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000503:physiopathology*; D009369:Neoplasms / Q000235:genetics / Q000503:physiopathology*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000503:physiopathology*; D009857:Oncogenes; D016601:RNA-Binding Proteins; D015398:Signal Transduction / Q000235:genetics
D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins