title: Overexpression of astrocyte elevated gene-1 (AEG-1) is associated with esophageal squamous cell carcinoma (ESCC) progression and pathogenesis.
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 (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.
authors.affiliation: 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.
authors.forename: Chunping
authors.initials: C
authors.lastname: Yu
authors.forename: Kun
authors.initials: K
authors.lastname: Chen
authors.forename: Haiqing
authors.initials: H
authors.lastname: Zheng
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Guo
authors.forename: Weihua
authors.initials: W
authors.lastname: Jia
authors.forename: Manzhi
authors.initials: M
authors.lastname: Li
authors.forename: Musheng
authors.initials: M
authors.lastname: Zeng
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Libing
authors.initials: L
authors.lastname: Song
mesh_terms: D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D017931:DNA Primers; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins; D009367:Neoplasm Staging; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D016601:RNA-Binding Proteins; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D015815:Cell Adhesion Molecules; D017931:DNA Primers; C483039:MTDH protein, human; D008565:Membrane Proteins; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins