Anterior gradient 2 regulates cancer progression in <em>TP53</em>‑wild‑type esophageal squamous cell carcinoma

Takabatake,Kazuya; Konishi,Hirotaka; Arita,Tomohiro; Kataoka,Satoshi; Shibamoto,Jun; Furuke,Hirotaka; Takaki,Wataru; Shoda,Katsutoshi; Shimizu,Hiroki; Yamamoto,Yusuke; Komatsu,Shuhei; Shiozaki,Atsushi; Fujiwara,Hitoshi; Okamoto,Kazuma; Otsuji,Eigo

doi:10.3892/or.2021.8211

Anterior gradient 2 regulates cancer progression in TP53‑wild‑type esophageal squamous cell carcinoma

Authors:
- Kazuya Takabatake
- Hirotaka Konishi
- Tomohiro Arita
- Satoshi Kataoka
- Jun Shibamoto
- Hirotaka Furuke
- Wataru Takaki
- Katsutoshi Shoda
- Hiroki Shimizu
- Yusuke Yamamoto
- Shuhei Komatsu
- Atsushi Shiozaki
- Hitoshi Fujiwara
- Kazuma Okamoto
- Eigo Otsuji
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Affiliations: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo‑ku, Kyoto 602-8566, Japan, First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan
Published online on: October 27, 2021 https://doi.org/10.3892/or.2021.8211
Article Number: 260

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Abstract

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 TP53‑wild‑type ESCC and osteosarcoma cells. However, these changes were not observed in TP53‑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 TP53‑wild‑type ESCC, the same mechanism did not regulate cell functions in TP53‑mutant ESCC. Thus, AGR2 served an important role in ESCC progression and might be a useful prognostic marker in patients with TP53‑wild‑type ESCC.

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