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

Abstract

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.

• Authors: Junmin Song, Seiji Futagami, Hiroyuki Nagoya, Tetsuro Kawagoe, Hiroshi Yamawaki, Yasuhiro Kodaka, Atsushi Tatsuguchi, Katya Gudis, Taiga Wakabayashi, Masaoki Yonezawa, Mayumi Shimpuku, Yasuhiko Watarai, Katsuhiko Iwakiri, Yoshio Hoshihara, Hiroshi Makino, Masao Miyashita, Shinichi Tsuchiya, Yan Li, Sheila E Crowe, Choitsu Sakamoto
• Journal: Journal of clinical biochemistry and nutrition (J Clin Biochem Nutr) Vol. 52 Issue 2 Pg. 112-9 (Mar 2013) ISSN: 0912-0009 [Print] Japan
• PMID: 23525727 (Publication Type: Journal Article)