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Article: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone promoted gastric cancer growth through prostaglandin E receptor (EP2 and EP4) in vivo and in vitro

Title4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone promoted gastric cancer growth through prostaglandin E receptor (EP2 and EP4) in vivo and in vitro
Authors
Issue Date2011
PublisherBlackwell Publishing Japan. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CAS
Citation
Cancer Science, 2011, v. 102 n. 5, p. 926-933 How to Cite?
AbstractProstaglandin E (EP) receptor is positively related with COX-2, which is involved in cancer biology. A mechanistic study on how 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) promotes gastric carcinogenesis is lacking. Recently, we found that nicotine promoted tumor growth through upregulation of the COX-2/prostaglandin E 2 pathway. This extended our study on the involvement of EP receptors in gastric carcinogenesis. Both in vitro and in vivo studies showed that NNK promoted cancer cell growth with concomitant EP2 and EP4 upregulation. We found that NNK stimulated vascular endothelial growth factor (VEGF) and angiogenesis, but suppressed apoptosis by increasing Bcl2 and decreasing caspase-3 expressions. Both EP2 and EP4 siRNA significantly impaired these tumorigenic actions of NNK in xenograft tumor. Cell cycle analysis showed that NNK increased S phase entry with increased cyclin D1 and the associated cyclin-dependent kinase 4/6, and downregulation of p21 and p27. The p38 phosphorylation was EP2/4-dependent, and SB203580 (p38 inhibitor) suppressed NNK-induced prostaglandin E 2, VEGF, and cell proliferation. Antagonists of EP2 or EP4 abolished the elevated VEGF and VEGF receptor-2. These data strongly indicate that EP2/4 are important for NNK-promoted gastric carcinogenesis, thus providing a framework for future evaluation of EP antagonist(s) as anticancer drugs for smokers. © 2011 Japanese Cancer Association.
Persistent Identifierhttp://hdl.handle.net/10722/133654
ISSN
2014 Impact Factor: 3.523
2014 SCImago Journal Rankings: 1.484
ISI Accession Number ID
Funding AgencyGrant Number
University of Hong Kong (Hong Kong, China)
Funding Information:

This work was supported by the small project funding from Committee on Research and Conference Grants, The University of Hong Kong (Hong Kong, China).

References

 

DC FieldValueLanguage
dc.contributor.authorShin, VYen_HK
dc.contributor.authorJin, HCen_HK
dc.contributor.authorNg, EKOen_HK
dc.contributor.authorCho, CHen_HK
dc.contributor.authorLeung, WKen_HK
dc.contributor.authorSung, JJYen_HK
dc.contributor.authorChu, KMen_HK
dc.date.accessioned2011-05-24T02:13:39Z-
dc.date.available2011-05-24T02:13:39Z-
dc.date.issued2011en_HK
dc.identifier.citationCancer Science, 2011, v. 102 n. 5, p. 926-933en_HK
dc.identifier.issn1347-9032en_HK
dc.identifier.urihttp://hdl.handle.net/10722/133654-
dc.description.abstractProstaglandin E (EP) receptor is positively related with COX-2, which is involved in cancer biology. A mechanistic study on how 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) promotes gastric carcinogenesis is lacking. Recently, we found that nicotine promoted tumor growth through upregulation of the COX-2/prostaglandin E 2 pathway. This extended our study on the involvement of EP receptors in gastric carcinogenesis. Both in vitro and in vivo studies showed that NNK promoted cancer cell growth with concomitant EP2 and EP4 upregulation. We found that NNK stimulated vascular endothelial growth factor (VEGF) and angiogenesis, but suppressed apoptosis by increasing Bcl2 and decreasing caspase-3 expressions. Both EP2 and EP4 siRNA significantly impaired these tumorigenic actions of NNK in xenograft tumor. Cell cycle analysis showed that NNK increased S phase entry with increased cyclin D1 and the associated cyclin-dependent kinase 4/6, and downregulation of p21 and p27. The p38 phosphorylation was EP2/4-dependent, and SB203580 (p38 inhibitor) suppressed NNK-induced prostaglandin E 2, VEGF, and cell proliferation. Antagonists of EP2 or EP4 abolished the elevated VEGF and VEGF receptor-2. These data strongly indicate that EP2/4 are important for NNK-promoted gastric carcinogenesis, thus providing a framework for future evaluation of EP antagonist(s) as anticancer drugs for smokers. © 2011 Japanese Cancer Association.en_HK
dc.languageengen_US
dc.publisherBlackwell Publishing Japan. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CASen_HK
dc.relation.ispartofCancer Scienceen_HK
dc.rightsThe definitive version is available at www.blackwell-synergy.com-
dc.subject.meshCarcinogens - toxicity-
dc.subject.meshNitrosamines - toxicity-
dc.subject.meshReceptors, Prostaglandin E, EP2 Subtype - metabolism-
dc.subject.meshReceptors, Prostaglandin E, EP4 Subtype - metabolism-
dc.subject.meshStomach Neoplasms - chemically induced - metabolism-
dc.title4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone promoted gastric cancer growth through prostaglandin E receptor (EP2 and EP4) in vivo and in vitroen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1347-9032&volume=102&issue=5&spage=926&epage=933&date=2011&atitle=4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone+promoted+gastric+cancer+growth+through+prostaglandin+E+receptor+(EP2+and+EP4)+in+vivo+and+in+vitro-
dc.identifier.emailNg, EKO: ngko@hku.hken_HK
dc.identifier.emailChu, KM: chukm@hkucc.hku.hken_HK
dc.identifier.authorityNg, EKO=rp01364en_HK
dc.identifier.authorityChu, KM=rp00435en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1349-7006.2011.01885.xen_HK
dc.identifier.pmid21261791en_HK
dc.identifier.scopuseid_2-s2.0-79954871936en_HK
dc.identifier.hkuros184334en_US
dc.identifier.hkuros199104-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79954871936&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume102en_HK
dc.identifier.issue5en_HK
dc.identifier.spage926en_HK
dc.identifier.epage933en_HK
dc.identifier.isiWOS:000289630300003-
dc.publisher.placeJapanen_HK
dc.identifier.scopusauthoridShin, VY=7003491170en_HK
dc.identifier.scopusauthoridJin, HC=24577511700en_HK
dc.identifier.scopusauthoridNg, EKO=21135553700en_HK
dc.identifier.scopusauthoridCho, CH=35228665500en_HK
dc.identifier.scopusauthoridLeung, WK=55218891800en_HK
dc.identifier.scopusauthoridSung, JJY=35405352400en_HK
dc.identifier.scopusauthoridChu, KM=7402453538en_HK

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