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Article: Haem oxygenase-1 plays a central role in NNK-mediated lung carcinogenesis

TitleHaem oxygenase-1 plays a central role in NNK-mediated lung carcinogenesis
Authors
Issue Date2008
Citation
European Respiratory Journal, 2008, v. 32 n. 4, p. 911-923 How to Cite?
AbstractThe tobacco-specific nitrosamine, 4-(N-methyl-N-nitrosoamino)-1-(3-pyridyl) -1-butanone (NNK), is a potent lung cancer inducer. However, how NNK induces lung cancer is still largely unknown. Haem oxygenase (HO)-1 was evaluated in 30 pairs of lung cancer tumour samples and matched nontumour tissues from patients with a history of cigarette smoking. Expression of HO-1, p21 Cip1/Waf1/Cid1 (p21), B-cell lymphoma (Bcl)-2 family members, mitogen-activated protein kinase and nuclear factor (NF)-κB was also studied in lung cancer cells treated with NNK. The levels of HO-1 and p21 were significantly increased in lung tumour tissues. There was a positive relationship between these two proteins in the tumour. NNK stimulated lung cell proliferation and elevated the levels of HO-1, p21, inhibitor of apoptosis protein (c-IAP)2 and Bcl-2, but downregulated Bad. These effects of NNK were blocked by zinc protoporphyrin-XII, an HO-1 inhibitor. The NNK-mediated expression of HO-1 was governed by NF-κB and extracellular signal-regulated kinase 1/2, since blocking either of these prevented the stimulatory effect of NNK on HO-1, as well as molecules downstream of HO-1, such as p21, c-IAP2, Bcl-2 and Bad. In conclusion, haem oxygenase-1 plays a central role in NNK-mediated cell proliferation by promoting the expression of p21 Cip1/Waf1/Cid1, inhibitor of apoptosis protein 2 and B-cell lymphoma-2 but inhibiting the activity of Bad. Nuclear factor-κB and extracellular signal-regulated kinase 1/2 function upstream of haem oxygenase-1. Therefore, haem oxygenase-1 is likely to be a potential target in the treatment of smoking-related lung cancer. Copyright©ERS Journals Ltd 2008.
Persistent Identifierhttp://hdl.handle.net/10722/192668
ISSN
2015 Impact Factor: 8.332
2015 SCImago Journal Rankings: 3.204
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, M-Yen_US
dc.contributor.authorYip, Jen_US
dc.contributor.authorHsin, MKYen_US
dc.contributor.authorMok, TSKen_US
dc.contributor.authorWu, Yen_US
dc.contributor.authorUnderwood, MJen_US
dc.contributor.authorChen, GGen_US
dc.date.accessioned2013-11-20T04:55:01Z-
dc.date.available2013-11-20T04:55:01Z-
dc.date.issued2008en_US
dc.identifier.citationEuropean Respiratory Journal, 2008, v. 32 n. 4, p. 911-923en_US
dc.identifier.issn0903-1936en_US
dc.identifier.urihttp://hdl.handle.net/10722/192668-
dc.description.abstractThe tobacco-specific nitrosamine, 4-(N-methyl-N-nitrosoamino)-1-(3-pyridyl) -1-butanone (NNK), is a potent lung cancer inducer. However, how NNK induces lung cancer is still largely unknown. Haem oxygenase (HO)-1 was evaluated in 30 pairs of lung cancer tumour samples and matched nontumour tissues from patients with a history of cigarette smoking. Expression of HO-1, p21 Cip1/Waf1/Cid1 (p21), B-cell lymphoma (Bcl)-2 family members, mitogen-activated protein kinase and nuclear factor (NF)-κB was also studied in lung cancer cells treated with NNK. The levels of HO-1 and p21 were significantly increased in lung tumour tissues. There was a positive relationship between these two proteins in the tumour. NNK stimulated lung cell proliferation and elevated the levels of HO-1, p21, inhibitor of apoptosis protein (c-IAP)2 and Bcl-2, but downregulated Bad. These effects of NNK were blocked by zinc protoporphyrin-XII, an HO-1 inhibitor. The NNK-mediated expression of HO-1 was governed by NF-κB and extracellular signal-regulated kinase 1/2, since blocking either of these prevented the stimulatory effect of NNK on HO-1, as well as molecules downstream of HO-1, such as p21, c-IAP2, Bcl-2 and Bad. In conclusion, haem oxygenase-1 plays a central role in NNK-mediated cell proliferation by promoting the expression of p21 Cip1/Waf1/Cid1, inhibitor of apoptosis protein 2 and B-cell lymphoma-2 but inhibiting the activity of Bad. Nuclear factor-κB and extracellular signal-regulated kinase 1/2 function upstream of haem oxygenase-1. Therefore, haem oxygenase-1 is likely to be a potential target in the treatment of smoking-related lung cancer. Copyright©ERS Journals Ltd 2008.en_US
dc.languageengen_US
dc.relation.ispartofEuropean Respiratory Journalen_US
dc.titleHaem oxygenase-1 plays a central role in NNK-mediated lung carcinogenesisen_US
dc.typeArticleen_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1183/09031936.00064508en_US
dc.identifier.pmid18508827-
dc.identifier.scopuseid_2-s2.0-58849110718en_US
dc.identifier.volume32en_US
dc.identifier.issue4en_US
dc.identifier.spage911en_US
dc.identifier.epage923en_US
dc.identifier.isiWOS:000259944500012-

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