| Subcellular localization of apurinic endonuclease 1 promotes lung tumor aggressiveness via NF-kappaB activation. | |
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MedLine Citation:
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PMID: 20498636 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Apurinic endonuclease 1 (Ape1) is not only involved in base excision repair, but also activates some transcriptional factors through its redox activity. However, which subcellular localization of Ape1 is involved in the activation of transcriptional factor remains unclear. We first observed that Cox-2 expression was associated with cytoplasmic Ape1 expression in lung tumors and cancer cell lines. We thus hypothesize that nuclear factor (NF)-kappaB is activated by cytoplasmic Ape1 to cause Cox-2 expression. Herein, we generated cytoplasmic and nuclear Ape1 in Ape1-knockdown lung cancer cells by exogenous expression of Ape1 containing various deletions and/or mutations of the nuclear localization sequence. It was observed that cytoplasmic Ape1, but not nuclear Ape1, induced Cox-2 expression through NF-kappaB activation. NF-kappaB activation by cytoplasmic Ape1 was diminished by the Ape1 redox activity inhibitor resveratrol. Cells expressing cytoplasmic Ape1 exhibited tumor progression and metastasis in vitro and in vivo as xenografts, but cells expressing nuclear Ape1 did not. Patients with tumors containing elevated cytoplasmic Ape1 had a poor prognosis and a 3.722-fold risk of tumor recurrence and/or metastasis. Cytoplasmic Ape1 could therefore enhance lung tumor malignancy through NF-kappaB activation, suggesting that combination of cisplatin and specific redox inhibitor could improve chemotherapeutic response in patients with tumors containing elevated cytoplasmic Ape1. |
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Authors:
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H-H Wu; Y-W Cheng; J T Chang; T-C Wu; W-S Liu; C-Y Chen; H Lee |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-24 |
Journal Detail:
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Title: Oncogene Volume: 29 ISSN: 1476-5594 ISO Abbreviation: Oncogene Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-29 Completed Date: 2010-08-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 4330-40 Citation Subset: IM |
Affiliation:
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Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, Republic of China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Nucleus / metabolism Cyclooxygenase 2 / biosynthesis Cytoplasm / metabolism DNA-(Apurinic or Apyrimidinic Site) Lyase / analysis, physiology* Female Humans Lung Neoplasms / enzymology, pathology* Mice Mice, Inbred BALB C NF-kappa B / physiology* Neoplasm Metastasis Prognosis Transcription Factor RelA / analysis Tumor Suppressor Protein p53 / metabolism |
| Chemical | |
Reg. No./Substance:
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0/NF-kappa B; 0/Transcription Factor RelA; 0/Tumor Suppressor Protein p53; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS2 protein, human; EC 4.2.99.18/APEX1 protein, human; EC 4.2.99.18/DNA-(Apurinic or Apyrimidinic Site) Lyase |
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