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Astrocyte Elevated Gene-1: Far More Than Just a Gene Regulated in Astrocytes

¹ Department of Human and Molecular Genetics, Virginia Commonwealth University; ² Virginia Commonwealth University Institute of Molecular Medicine, Virginia Commonwealth University; ³ Virginia Commonwealth University Massey Cancer Center, Virginia Commonwealth University, School of Medicine, Richmond, Virginia; and ⁴ Department of Neurosurgery, Mount Sinai School of Medicine, New York, New York

Requests for reprints: Paul B. Fisher, Virginia Commonwealth University, School of Medicine, 1101 East Marshall Street, Sanger Hall Building, Room 11-015, Richmond, VA 23298. Phone: 804-828-9632; Fax: 804-827-1124; E-mail: pbfisher{at}vcu.edu and Devanand Sarkar, Virginia Commonwealth University, School of Medicine, 1220 E. Broad St., P.O. Box 980035, Richmond, VA 23298. Phone: 804-827-2339; Fax: 804-628-1176; E-mail: dsarkar{at}vcu.edu.

Since its original cloning by subtraction hybridization in 2002, it is now evident that Astrocyte elevated gene-1 (AEG-1) is a key contributor to the carcinogenic process in diverse organs. AEG-1 protein expression is elevated in advanced stages of many cancers, which correlates with poor survival. In specific cancers, such as breast and liver cancer, the AEG-1 gene itself is amplified, further supporting a seminal role in tumorigenesis. Overexpression and inhibition studies both in in vitro and in in vivo models reveal the importance of AEG-1 in regulating multiple physiologically and pathologically relevant processes including proliferation, invasion, metastasis, and gene expression. AEG-1 is a single-pass transmembrane protein with multiple nuclear localization signals and no known domains or motifs. Although pertinent roles of AEG-1 in the carcinogenic process are established, its potential function (promotion of metastasis only versus functioning as a bona fide oncogene) as well as localization (cell surface versus nucleus) remain areas requiring further clarification. The present review critically evaluates what is currently known about AEG-1 and provides new perspectives relative to this intriguing molecule that may provide a rational target for intervening in the cancer phenotype. [Cancer Res 2009;69(22):8529–35]