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

作者：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

来源：Journal of Clinical Biochemistry and Nutrition, 2013, 52(2): 112-119.

DOI：10.3164/jcbn.12-95

• APE-1
• esophageal squamous cell carcinoma
• NF-kappa B-p65
• p65-NLS
• MCP-1

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-kappa B pathway in ESCC tissue.

• 出版日期2013-3-1
• 单位中国医科大学