Carcinogenesis Advance Access originally published online on March 20, 2009
Carcinogenesis 2009 30(5):894-901; doi:10.1093/carcin/bgp064
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Overexpression of astrocyte elevated gene-1 (AEG-1) is associated with esophageal squamous cell carcinoma (ESCC) progression and pathogenesis
State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, People's Republic of China
1 Department of Neurosurgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China
2 Department of Rehabilitation Medicine, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510065, China
3 Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou, Guangdong 510080, People's Republic of China
* To whom correspondence should be addressed. Tel: +86 20 87343192; Fax: +86 2087343171; Email: lb.song1{at}gmail.com
Correspondence may also be addressed to Jun Li. Tel: +86 20 87335793; Fax: +86 20 87331209; Email: junli99{at}gmail.com
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 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.
Abbreviations: AEG-1, astrocyte- elevated gene-1; ESCC, esophageal squamous cell carcinoma; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; MOD, mean optical density; NEEC, normal esophageal epithelial cell; PCR, polymerase chain reaction; SI, staining index
These authors contributed equally to this work. Received December 20, 2008; revised March 16, 2009; accepted March 16, 2009.
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