Apurinic/apyrimidinic endonuclease-1 (APE-1) is overexpressed via the activation of NF-κB-p65 in MCP-1-positive esophageal squamous cell carcinoma tissue

• Published in: Journal of Clinical Biochemistry and Nutrition Vol. 52; no. 2; pp. 112 - 119
• Main Authors: Song, Junmin, Futagami, Seiji, Nagoya, Hiroyuki, Kawagoe, Tetsuro, Yamawaki, Hiroshi, Kodaka, Yasuhiro, Tatsuguchi, Atsushi, Gudis, Katya, Wakabayashi, Taiga, Yonezawa, Masaoki, Shimpuku, Mayumi, Watarai, Yasuhiko, Iwakiri, Katsuhiko, Hoshihara, Yoshio, Makino, Hiroshi, Miyashita, Masao, Tsuchiya, Shinichi, Li, Yan, Crowe, Sheila E., Sakamoto, Choitsu
• Format: Journal Article
• Language: English
• Published: Japan SOCIETY FOR FREE RADICAL RESEARCH JAPAN 01.03.2013; the Society for Free Radical Research Japan
• Subjects: APE-1; esophageal squamous cell carcinoma; MCP-1; NF-κB-p65; Original; p65-NLS; esophageal squamous cell carcinoma; MCP-1; APE-1; NF-κB-p65; p65-NLS
• ISSN: 0912-0009; 1880-5086
• DOI: 10.3164/jcbn.12-95

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.