File Download
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone promoted gastric cancer growth through prostaglandin E receptor (EP2 and EP4) in vivo and in vitro
  • Basic View
  • Metadata View
  • XML View
Title4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone promoted gastric cancer growth through prostaglandin E receptor (EP2 and EP4) in vivo and in vitro
 
AuthorsShin, VY1
Jin, HC2
Ng, EKO1
Cho, CH3
Leung, WK3
Sung, JJY3
Chu, KM1
 
Issue Date2011
 
PublisherBlackwell Publishing Japan. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CAS
 
CitationCancer Science, 2011, v. 102 n. 5, p. 926-933 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1349-7006.2011.01885.x
 
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.
 
ISSN1347-9032
 
DOIhttp://dx.doi.org/10.1111/j.1349-7006.2011.01885.x
 
ISI Accession Number IDWOS:000289630300003
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).

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorShin, VY
 
dc.contributor.authorJin, HC
 
dc.contributor.authorNg, EKO
 
dc.contributor.authorCho, CH
 
dc.contributor.authorLeung, WK
 
dc.contributor.authorSung, JJY
 
dc.contributor.authorChu, KM
 
dc.date.accessioned2011-05-24T02:13:39Z
 
dc.date.available2011-05-24T02:13:39Z
 
dc.date.issued2011
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationCancer Science, 2011, v. 102 n. 5, p. 926-933 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1349-7006.2011.01885.x
 
dc.identifier.doihttp://dx.doi.org/10.1111/j.1349-7006.2011.01885.x
 
dc.identifier.epage933
 
dc.identifier.hkuros184334
 
dc.identifier.hkuros199104
 
dc.identifier.isiWOS:000289630300003
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).

 
dc.identifier.issn1347-9032
 
dc.identifier.issue5
 
dc.identifier.openurl
 
dc.identifier.pmid21261791
 
dc.identifier.scopuseid_2-s2.0-79954871936
 
dc.identifier.spage926
 
dc.identifier.urihttp://hdl.handle.net/10722/133654
 
dc.identifier.volume102
 
dc.languageeng
 
dc.publisherBlackwell Publishing Japan. The Journal's web site is located at http://www.blackwellpublishing.com/journals/CAS
 
dc.publisher.placeJapan
 
dc.relation.ispartofCancer Science
 
dc.relation.referencesReferences in Scopus
 
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 vitro
 
dc.typeArticle
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Shin, VY</contributor.author>
<contributor.author>Jin, HC</contributor.author>
<contributor.author>Ng, EKO</contributor.author>
<contributor.author>Cho, CH</contributor.author>
<contributor.author>Leung, WK</contributor.author>
<contributor.author>Sung, JJY</contributor.author>
<contributor.author>Chu, KM</contributor.author>
<date.accessioned>2011-05-24T02:13:39Z</date.accessioned>
<date.available>2011-05-24T02:13:39Z</date.available>
<date.issued>2011</date.issued>
<identifier.citation>Cancer Science, 2011, v. 102 n. 5, p. 926-933</identifier.citation>
<identifier.issn>1347-9032</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/133654</identifier.uri>
<description.abstract>Prostaglandin 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. &#169; 2011 Japanese Cancer Association.</description.abstract>
<language>eng</language>
<publisher>Blackwell Publishing Japan. The Journal&apos;s web site is located at http://www.blackwellpublishing.com/journals/CAS</publisher>
<relation.ispartof>Cancer Science</relation.ispartof>
<rights>The definitive version is available at www.blackwell-synergy.com</rights>
<subject.mesh>Carcinogens - toxicity</subject.mesh>
<subject.mesh>Nitrosamines - toxicity</subject.mesh>
<subject.mesh>Receptors, Prostaglandin E, EP2 Subtype - metabolism</subject.mesh>
<subject.mesh>Receptors, Prostaglandin E, EP4 Subtype - metabolism</subject.mesh>
<subject.mesh>Stomach Neoplasms - chemically induced - metabolism</subject.mesh>
<title>4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone promoted gastric cancer growth through prostaglandin E receptor (EP2 and EP4) in vivo and in vitro</title>
<type>Article</type>
<identifier.openurl>http://library.hku.hk:4550/resserv?sid=HKU:IR&amp;issn=1347-9032&amp;volume=102&amp;issue=5&amp;spage=926&amp;epage=933&amp;date=2011&amp;atitle=4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone+promoted+gastric+cancer+growth+through+prostaglandin+E+receptor+(EP2+and+EP4)+in+vivo+and+in+vitro</identifier.openurl>
<description.nature>Link_to_subscribed_fulltext</description.nature>
<identifier.doi>10.1111/j.1349-7006.2011.01885.x</identifier.doi>
<identifier.pmid>21261791</identifier.pmid>
<identifier.scopus>eid_2-s2.0-79954871936</identifier.scopus>
<identifier.hkuros>184334</identifier.hkuros>
<identifier.hkuros>199104</identifier.hkuros>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-79954871936&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>102</identifier.volume>
<identifier.issue>5</identifier.issue>
<identifier.spage>926</identifier.spage>
<identifier.epage>933</identifier.epage>
<identifier.isi>WOS:000289630300003</identifier.isi>
<publisher.place>Japan</publisher.place>
</item>
Author Affiliations
  1. The University of Hong Kong
  2. Zhejiang University
  3. Chinese University of Hong Kong