PMID- 23525727 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20130326 LR - 20211021 IS - 0912-0009 (Print) IS - 1880-5086 (Electronic) IS - 0912-0009 (Linking) VI - 52 IP - 2 DP - 2013 Mar TI - Apurinic/apyrimidinic endonuclease-1 (APE-1) is overexpressed via the activation of NF-kappaB-p65 in MCP-1-positive esophageal squamous cell carcinoma tissue. PG - 112-9 LID - 10.3164/jcbn.12-95 [doi] AB - 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-kappaB pathway in ESCC tissue. FAU - Song, Junmin AU - Song J AD - 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. FAU - Futagami, Seiji AU - Futagami S FAU - Nagoya, Hiroyuki AU - Nagoya H FAU - Kawagoe, Tetsuro AU - Kawagoe T FAU - Yamawaki, Hiroshi AU - Yamawaki H FAU - Kodaka, Yasuhiro AU - Kodaka Y FAU - Tatsuguchi, Atsushi AU - Tatsuguchi A FAU - Gudis, Katya AU - Gudis K FAU - Wakabayashi, Taiga AU - Wakabayashi T FAU - Yonezawa, Masaoki AU - Yonezawa M FAU - Shimpuku, Mayumi AU - Shimpuku M FAU - Watarai, Yasuhiko AU - Watarai Y FAU - Iwakiri, Katsuhiko AU - Iwakiri K FAU - Hoshihara, Yoshio AU - Hoshihara Y FAU - Makino, Hiroshi AU - Makino H FAU - Miyashita, Masao AU - Miyashita M FAU - Tsuchiya, Shinichi AU - Tsuchiya S FAU - Li, Yan AU - Li Y FAU - E Crowe, Sheila AU - E Crowe S FAU - Sakamoto, Choitsu AU - Sakamoto C LA - eng PT - Journal Article DEP - 20130301 PL - Japan TA - J Clin Biochem Nutr JT - Journal of clinical biochemistry and nutrition JID - 8700907 PMC - PMC3593127 OTO - NOTNLM OT - APE-1 OT - MCP-1 OT - NF-kappaB-p65 OT - esophageal squamous cell carcinoma OT - p65-NLS EDAT- 2013/03/26 06:00 MHDA- 2013/03/26 06:01 PMCR- 2013/03/01 CRDT- 2013/03/26 06:00 PHST- 2012/08/31 00:00 [received] PHST- 2012/12/18 00:00 [accepted] PHST- 2013/03/26 06:00 [entrez] PHST- 2013/03/26 06:00 [pubmed] PHST- 2013/03/26 06:01 [medline] PHST- 2013/03/01 00:00 [pmc-release] AID - jcbn12-95 [pii] AID - 10.3164/jcbn.12-95 [doi] PST - ppublish SO - J Clin Biochem Nutr. 2013 Mar;52(2):112-9. doi: 10.3164/jcbn.12-95. Epub 2013 Mar 1.