Anterior gradient 2 (AGR2) reportedly promotes tumor growth and has an unfavorable impact on survival in several cancers. However, no comprehensive functional analysis of AGR2 in esophageal squamous cell carcinoma (ESCC) has been performed. In the present study, the function and clinical significance of AGR2 were examined using ESCC cell lines and clinical samples. AGR2 was upregulated in EC tissue and ESCC cell lines. The downregulation of AGR2 suppressed cell proliferation and increased the proportion of G2/M‑phase cells and phosphorylation of p53 in ‑wild‑type ESCC and osteosarcoma cells. However, these changes were not observed in ‑mutant ESCC cells. In addition, immunohistochemistry results demonstrated that high AGR2 and low p53 expression levels in ESCC tissues were correlated with a worse prognosis. These results suggested that although AGR2 enhanced cell proliferation by inhibiting p53 phosphorylation in ‑wild‑type ESCC, the same mechanism did not regulate cell functions in ‑mutant ESCC. Thus, AGR2 served an important role in ESCC progression and might be a useful prognostic marker in patients with ‑wild‑type ESCC.
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