Sarkar Devanand, Emdad Luni, Lee Seok-Geun, Yoo Byoung Kwon, Su Zao-Zhong, Fisher Paul B
Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Cancer Res. 2009 Nov 15;69(22):8529-35. doi: 10.1158/0008-5472.CAN-09-1846. Epub 2009 Nov 10.
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.
自2002年通过消减杂交首次克隆以来，现已明确星形胶质细胞上调基因-1（AEG-1）是多种器官致癌过程的关键促成因素。AEG-1蛋白表达在许多癌症的晚期升高，这与较差的生存率相关。在特定癌症中，如乳腺癌和肝癌，AEG-1基因本身会扩增，进一步支持其在肿瘤发生中的重要作用。体外和体内模型中的过表达和抑制研究均揭示了AEG-1在调节包括增殖、侵袭、转移和基因表达在内的多种生理和病理相关过程中的重要性。AEG-1是一种单次跨膜蛋白，具有多个核定位信号，没有已知的结构域或基序。尽管AEG-1在致癌过程中的相关作用已得到确立，但其潜在功能（仅促进转移还是作为真正的癌基因发挥作用）以及定位（细胞表面还是细胞核）仍有待进一步阐明。本综述批判性地评估了目前关于AEG-1的已知信息，并提供了关于这个有趣分子的新观点，这可能为干预癌症表型提供合理的靶点。
