Linked Life Data

20498636

Source:http://linkedlifedata.com/resource/pubmed/id/20498636

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
30
pubmed:dateCreated
2010-7-29
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1476-5594
pubmed:author
pubmed:issnType
Electronic
pubmed:day
29
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4330-40
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Subcellular localization of apurinic endonuclease 1 promotes lung tumor aggressiveness via NF-kappaB activation.
pubmed:affiliation
Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't