Overexpression of astrocyte elevated gene-1 (AEG-1) is associated with esophageal squamous cell carcinoma (ESCC) progression and pathogenesis
Overexpression of astrocyte elevated gene-1 (AEG-1) is associated with esophageal squamous cell carcinoma (ESCC) progression and pathogenesis
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星形胶质细胞升高基因 1 (AEG-1) 的过度表达与食管鳞状细胞癌 (ESCC) 的进展和发病机制相关
DOI：
10.1093/carcin/bgp064
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发表时间：
2009-05-01
期刊：
影响因子：
4.7
通讯作者：
Song, Libing
中科院分区：
文献类型：
--
作者：
Yu, Chunping;Chen, Kun;Song, Libing
星形胶质细胞升高基因-1（AEG-1）在多种人类癌症中表达上调，已被报道与人类癌症的发生有关。然而，AEG-1在人食管鳞状细胞癌（ESCC）中的功能意义仍不清楚。在本研究中，我们发现AEG-1在食管癌细胞系和手术ESCC标本中的表达在转录和翻译水平上均显著上调。免疫组化分析显示，80 168（47.6%）石蜡包埋档案ESCC标本表现出高水平的AEG-1表达。AEG-1的表达与食管鳞癌的临床分期密切相关（P = 0.001），T分类（P = 0.002），N分类（P = 0.034），M分类AEG-1高表达者生存期短（P < 0.001）。多因素分析提示AEG-1表达可能是食管鳞癌患者生存的独立预后指标。此外，我们发现AEG-1在ESCC细胞中的异位表达可显著增强细胞增殖和非贴壁依赖性生长能力。相反，通过短发夹RNA干扰沉默AEG-1导致细胞生长和软琼脂上的锚定非依赖性生长能力的抑制。此外，我们证明，AEG-1的上调可以通过AKT/FOXO 3a途径降低p27（Kip 1）的表达并诱导cyclin D1的表达。我们的研究结果表明AEG-1蛋白是ESCC进展的一个有价值的标志物，并且AEG-1的上调在人类ESCC的发展和发病机制中起着重要作用。
Astrocyte elevated gene-1 (AEG-1), upregulated in various types of human cancers, has been reported to be associated with the carcinogenesis of human cancer. However, the functional significance of AEG-1 in human esophageal squamous cell carcinoma (ESCC) remains unknown. In the present study, we showed the expression of AEG-1 was markedly upregulated in esophageal cancer cell lines and surgical ESCC specimens at both transcriptional and translational levels. Immunohistochemical analysis revealed that 80 of 168 (47.6%) paraffin-embedded archival ESCC specimens exhibited high levels of AEG-1 expression. Statistical analysis suggested the upregulation of AEG-1 was significantly correlated with the clinical staging of the ESCC patients (P = 0.001), T classification (P = 0.002), N classification (P = 0.034), M classification (P = 0.021) and histological differentiation (P = 0.035) and those patients with high AEG-1 levels exhibited shorter survival time (P < 0.001). Multivariate analysis indicated that AEG-1 expression might be an independent prognostic indicator of the survival of patients with ESCC. Furthermore, we found that ectopic expression of AEG-1 in ESCC cells could significantly enhance cell proliferation and anchorage-independent growth ability. Conversely, silencing AEG-1 by short hairpin RNAi caused an inhibition of cell growth and anchorage-independent growth ability on soft agar. Moreover, we demonstrated that the upregulation of AEG-1 could reduce the expression of p27(Kip1) and induce the expression of cyclin D1 through the AKT/FOXO3a pathway. Our findings suggest that the AEG-1 protein is a valuable marker of ESCC progression and that the upregulation of AEG-1 plays an important role in the development and pathogenesis of human ESCC.