Document Detail

Subcellular localization of apurinic endonuclease 1 promotes lung tumor aggressiveness via NF-kappaB activation.
MedLine Citation:
PMID:  20498636     Owner:  NLM     Status:  MEDLINE    
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.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-24
Journal Detail:
Title:  Oncogene     Volume:  29     ISSN:  1476-5594     ISO Abbreviation:  Oncogene     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-29     Completed Date:  2010-08-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  4330-40     Citation Subset:  IM    
Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, Republic of China.
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MeSH Terms
Cell Nucleus / metabolism
Cyclooxygenase 2 / biosynthesis
Cytoplasm / metabolism
DNA-(Apurinic or Apyrimidinic Site) Lyase / analysis,  physiology*
Lung Neoplasms / enzymology,  pathology*
Mice, Inbred BALB C
NF-kappa B / physiology*
Neoplasm Metastasis
Transcription Factor RelA / analysis
Tumor Suppressor Protein p53 / metabolism
Reg. No./Substance:
0/NF-kappa B; 0/Transcription Factor RelA; 0/Tumor Suppressor Protein p53; EC 2; EC protein, human; EC protein, human; EC or Apyrimidinic Site) Lyase

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