Apurinic/apyrimidinic endonuclease-1 (APE-1) is overexpressed via the activation of NF-κB-p65 in MCP-1-positive esophageal squamous cell carcinoma tissue
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- Song Junmin
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School Department of Gastroenterology, Shengjing Hospital, China Medical University
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- Futagami Seiji
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School
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- Nagoya Hiroyuki
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School
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- Kawagoe Tetsuro
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School
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- Yamawaki Hiroshi
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School
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- Kodaka Yasuhiro
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School
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- Tatsuguchi Atsushi
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School
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- Gudis Katya
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School
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- Wakabayashi Taiga
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School
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- Yonezawa Masaoki
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School
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- Shimpuku Mayumi
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School
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- Watarai Yasuhiko
- Division of Diagnostic Pathology, Nippon Medical School Hospital
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- Iwakiri Katsuhiko
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School
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- Hoshihara Yoshio
- Clinic of the Ministry of Economy, Trade and Industry
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- Makino Hiroshi
- Department of Surgery, Nippon Medical School
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- Miyashita Masao
- Department of Surgery, Nippon Medical School
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- Tsuchiya Shinichi
- Division of Diagnostic Pathology, Nippon Medical School Hospital
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- Li Yan
- Department of Gastroenterology, Shengjing Hospital, China Medical University
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- E. Crowe Sheila
- Division of Gastroenterology, Department of Medicine, University of California
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- Sakamoto Choitsu
- Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School
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抄録
Apurinic/apyrimidinic endonuclease-1 (APE-1), a key enzyme responsible for DNA base excision repair (BER), has been linked to cancer chemoradiosensitivity. The phosphorylation of p65 plays a role in the activation of this pathway. In this study, we investigated APE-1 expression and its interaction with p65 in esophageal squamous cell carcinoma (ESCC) tissue. The expression of APE-1, p65, p65 nuclear localization sequence (p65-NLS), and monocyte chemoattractant protein-1 (MCP-1) was assessed by immunohistochemical analysis in 67 human ESCC tissue samples. Real-time PCR and western blotting were also performed. p65 siRNA was evaluated to determine the role of p65 in the regulation of APE-1 expression. We found nuclear localization of APE-1 in 89.6% (60/67) of ESCC tissue samples. We also observed the colocalization of p65-NLS and APE-1 in esophageal cancer tissue. In KYSE220 cells, pretreatment of MG-132 significantly abrogated upregulation of p65 and APE-1 levels induced by MCP-1, and treatment with 10 and 20 nM p65 siRNA significantly inhibited APE-1 mRNA expression. siRNA for p65 treatment significantly increased the apoptotic index in 5-FU-treated KYSE220 cells. We conclude that APE-1 is overexpressed and mainly localized in the nuclear compartment of cancer cells, and partly regulated by p65 in the NF-κB pathway in ESCC tissue.
収録刊行物
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- Ｊｏｕｒｎａｌ ｏｆ Ｃｌｉｎｉｃａｌ Ｂｉｏｃｈｅｍｉｓｔｒｙ ａｎｄ Ｎｕｔｒｉｔｉｏｎ
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Ｊｏｕｒｎａｌ ｏｆ Ｃｌｉｎｉｃａｌ Ｂｉｏｃｈｅｍｉｓｔｒｙ ａｎｄ Ｎｕｔｒｉｔｉｏｎ 52 (2), 112-119, 2013
一般社団法人 日本酸化ストレス学会
