title: 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.affiliation: Division of Gastroenterology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan ; Department of Gastroenterology, Shengjing Hospital, China Medical University, Sanhao Street 36, Heping District, Shenyang, 110004, P.R. China.
authors.forename: Junmin
authors.initials: J
authors.lastname: Song
authors.forename: Seiji
authors.initials: S
authors.lastname: Futagami
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagoya
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kawagoe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamawaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tatsuguchi
authors.forename: Katya
authors.initials: K
authors.lastname: Gudis
authors.forename: Taiga
authors.initials: T
authors.lastname: Wakabayashi
authors.forename: Masaoki
authors.initials: M
authors.lastname: Yonezawa
authors.forename: Mayumi
authors.initials: M
authors.lastname: Shimpuku
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Watarai
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Iwakiri
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hoshihara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Makino
authors.forename: Masao
authors.initials: M
authors.lastname: Miyashita
authors.forename: Shinichi
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Sheila
authors.initials: S
authors.lastname: E Crowe
authors.forename: Choitsu
authors.initials: C
authors.lastname: Sakamoto
keywords: APE-1; MCP-1; NF-κB-p65; esophageal squamous cell carcinoma; p65-NLS