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- Title
Overexpression of astrocyte elevated gene-1 (AEG-1) is associated with esophageal squamous cell carcinoma (ESCC) progression and pathogenesis.
- Authors
Yu, Chunping; Chen, Kun; Zheng, Haiqing; Guo, Xianzhi; Jia, Weihua; Li, ManZhi; Zeng, Musheng; Li, Jun; Song, Libing
- Abstract
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 (Pâ=â0.001), T classification (Pâ=â0.002), N classification (Pâ=â0.034), M classification (Pâ=â0.021) and histological differentiation (Pâ=â0.035) and those patients with high AEG-1 levels exhibited shorter survival time (Pâ<â0.001). 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 p27Kip1 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.
- Subjects
GENE expression; ASTROCYTES; SQUAMOUS cell carcinoma; ESOPHAGEAL cancer; CARCINOGENESIS; GENE silencing; TUMOR markers; GENETICS
- Publication
Carcinogenesis, 2009, Vol 30, Issue 5, p894
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgp064