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Article: 4-Methylnitrosamino-1-3-pyridyl-1-butanone (NNK) promotes lung cancer cell survival by stimulating thromboxane A 2 and its receptor

Title4-Methylnitrosamino-1-3-pyridyl-1-butanone (NNK) promotes lung cancer cell survival by stimulating thromboxane A 2 and its receptor
Authors
Issue Date2011
Citation
Oncogene, 2011, v. 30 n. 1, p. 106-116 How to Cite?
AbstractThe role of thromboxane A2 (TxA2) in smoking-associated lung cancer is poorly understood. This study was conducted to study the role of TxA2 in smoking carcinogen 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK)-promoted cell survival and growth in human lung cancer cells. We found that NNK increased TxA2 synthase (TxAS) expression and thromboxane B 2 (TxB 2) generation in cultured lung cancer cells, the result of which was supported by the increased level of TxAS in lung cancer tissues of smokers. Both TxAS-specific inhibitor furegrelate and TxA 2 receptor antagonist SQ29548 completely blocked NNK-mediated cell survival and growth via inducting apoptosis. TxA2 receptor agonist U46619 reconstituted a near-full survival and growth response to NNK when TxAS was inhibited, affirming the role of TxA2 receptor in NNK-mediated cell survival and growth. Suppression of cyclic adenosine monophosphate response element binding protein (CREB) activity by its small interference RNA blocked the effect of NNK. Phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) also had a positive role. Altogether, our results have revealed that NNK stimulates TxA2 synthesis and activates its receptor in lung cancer cells. The increased TxA2 may then activate CREB through PI3K/Akt and extracellular ERK pathways, thereby contributing to the NNK-promoted survival and growth of lung cancer cells. © 2011 Macmillan Publishers Limited All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/192682
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHuang, R-Yen_US
dc.contributor.authorLi, M-Yen_US
dc.contributor.authorHsin, MKYen_US
dc.contributor.authorUnderwood, MJen_US
dc.contributor.authorMa, LTen_US
dc.contributor.authorMok, TSKen_US
dc.contributor.authorWarner, TDen_US
dc.contributor.authorChen, GGen_US
dc.date.accessioned2013-11-20T04:55:15Z-
dc.date.available2013-11-20T04:55:15Z-
dc.date.issued2011en_US
dc.identifier.citationOncogene, 2011, v. 30 n. 1, p. 106-116en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttp://hdl.handle.net/10722/192682-
dc.description.abstractThe role of thromboxane A2 (TxA2) in smoking-associated lung cancer is poorly understood. This study was conducted to study the role of TxA2 in smoking carcinogen 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK)-promoted cell survival and growth in human lung cancer cells. We found that NNK increased TxA2 synthase (TxAS) expression and thromboxane B 2 (TxB 2) generation in cultured lung cancer cells, the result of which was supported by the increased level of TxAS in lung cancer tissues of smokers. Both TxAS-specific inhibitor furegrelate and TxA 2 receptor antagonist SQ29548 completely blocked NNK-mediated cell survival and growth via inducting apoptosis. TxA2 receptor agonist U46619 reconstituted a near-full survival and growth response to NNK when TxAS was inhibited, affirming the role of TxA2 receptor in NNK-mediated cell survival and growth. Suppression of cyclic adenosine monophosphate response element binding protein (CREB) activity by its small interference RNA blocked the effect of NNK. Phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK) also had a positive role. Altogether, our results have revealed that NNK stimulates TxA2 synthesis and activates its receptor in lung cancer cells. The increased TxA2 may then activate CREB through PI3K/Akt and extracellular ERK pathways, thereby contributing to the NNK-promoted survival and growth of lung cancer cells. © 2011 Macmillan Publishers Limited All rights reserved.en_US
dc.languageengen_US
dc.relation.ispartofOncogeneen_US
dc.title4-Methylnitrosamino-1-3-pyridyl-1-butanone (NNK) promotes lung cancer cell survival by stimulating thromboxane A 2 and its receptoren_US
dc.typeArticleen_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/onc.2010.390en_US
dc.identifier.pmid20818420-
dc.identifier.scopuseid_2-s2.0-78650980124en_US
dc.identifier.volume30en_US
dc.identifier.issue1en_US
dc.identifier.spage106en_US
dc.identifier.epage116en_US
dc.identifier.isiWOS:000285959300010-

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