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Article: Catalytic activity of matrix metalloproteinase-19 is essential for tumor suppressor and anti-angiogenic activities in nasopharyngeal carcinoma

TitleCatalytic activity of matrix metalloproteinase-19 is essential for tumor suppressor and anti-angiogenic activities in nasopharyngeal carcinoma
Authors
Keywordsangiogenesis
MMP19
nasopharyngeal carcinoma
tumor suppressor gene
Issue Date2011
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
Citation
International Journal Of Cancer, 2011, v. 129 n. 8, p. 1826-1837 How to Cite?
AbstractThe association of Matrix metalloproteinase-19 (MMP19) in the development of nasopharyngeal carcinoma (NPC) was identified from differential gene profiling, which showed MMP19 was one of the candidate genes down-regulated in the NPC cell lines. In this study, quantitative RT-PCR and Western blot analysis showed MMP19 was down-regulated in all seven NPC cell lines. By tissue microarray immunohistochemical staining, MMP19 appears down-regulated in 69.7% of primary NPC specimens. Allelic deletion and promoter hypermethylation contribute to MMP19 down-regulation. We also clearly demonstrate that the catalytic activity of MMP19 plays an important role in antitumor and antiangiogenesis activities in comparative studies of the wild-type and the catalytically inactive mutant MMP19. In the in vivo tumorigenicity assay, only the wild-type (WT), but not mutant, MMP19 transfectants suppress tumor formation in nude mice. In the in vitro colony formation assay, WT MMP19 dramatically reduces colony-forming ability of NPC cell lines, when compared to the inactive mutant. In the tube formation assay of human umbilical vein endothelial cells and human microvascular endothelial cells (HMEC-1), secreted WT MMP19, but not mutant MMP19, induces reduction of tube-forming ability in endothelial cells with decreased vascular endothelial growth factor (VEGF) in conditioned media detected by enzyme-linked immunosorbent assay (ELISA). The anti-angiogenic activity of WT MMP19 is correlated with suppression of tumor formation. These results now clearly show that catalytic activity of MMP19 is essential for its tumor suppressive and anti-angiogenic functions in NPC. Copyright © 2010 UICC.
Persistent Identifierhttp://hdl.handle.net/10722/135083
ISSN
2014 Impact Factor: 5.085
2014 SCImago Journal Rankings: 2.175
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, KCen_HK
dc.contributor.authorKo, JMYen_HK
dc.contributor.authorLung, HLen_HK
dc.contributor.authorSedlacek, Ren_HK
dc.contributor.authorZhang, ZFen_HK
dc.contributor.authorLuo, DZen_HK
dc.contributor.authorFeng, ZBen_HK
dc.contributor.authorChen, Sen_HK
dc.contributor.authorChen, Hen_HK
dc.contributor.authorChan, KWen_HK
dc.contributor.authorTsao, SWen_HK
dc.contributor.authorChua, DTTen_HK
dc.contributor.authorZabarovsky, ERen_HK
dc.contributor.authorStanbridge, EJen_HK
dc.contributor.authorLung, MLen_HK
dc.date.accessioned2011-07-27T01:27:47Z-
dc.date.available2011-07-27T01:27:47Z-
dc.date.issued2011en_HK
dc.identifier.citationInternational Journal Of Cancer, 2011, v. 129 n. 8, p. 1826-1837en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/135083-
dc.description.abstractThe association of Matrix metalloproteinase-19 (MMP19) in the development of nasopharyngeal carcinoma (NPC) was identified from differential gene profiling, which showed MMP19 was one of the candidate genes down-regulated in the NPC cell lines. In this study, quantitative RT-PCR and Western blot analysis showed MMP19 was down-regulated in all seven NPC cell lines. By tissue microarray immunohistochemical staining, MMP19 appears down-regulated in 69.7% of primary NPC specimens. Allelic deletion and promoter hypermethylation contribute to MMP19 down-regulation. We also clearly demonstrate that the catalytic activity of MMP19 plays an important role in antitumor and antiangiogenesis activities in comparative studies of the wild-type and the catalytically inactive mutant MMP19. In the in vivo tumorigenicity assay, only the wild-type (WT), but not mutant, MMP19 transfectants suppress tumor formation in nude mice. In the in vitro colony formation assay, WT MMP19 dramatically reduces colony-forming ability of NPC cell lines, when compared to the inactive mutant. In the tube formation assay of human umbilical vein endothelial cells and human microvascular endothelial cells (HMEC-1), secreted WT MMP19, but not mutant MMP19, induces reduction of tube-forming ability in endothelial cells with decreased vascular endothelial growth factor (VEGF) in conditioned media detected by enzyme-linked immunosorbent assay (ELISA). The anti-angiogenic activity of WT MMP19 is correlated with suppression of tumor formation. These results now clearly show that catalytic activity of MMP19 is essential for its tumor suppressive and anti-angiogenic functions in NPC. Copyright © 2010 UICC.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_HK
dc.relation.ispartofInternational Journal of Canceren_HK
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc..-
dc.subjectangiogenesisen_HK
dc.subjectMMP19en_HK
dc.subjectnasopharyngeal carcinomaen_HK
dc.subjecttumor suppressor geneen_HK
dc.titleCatalytic activity of matrix metalloproteinase-19 is essential for tumor suppressor and anti-angiogenic activities in nasopharyngeal carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.emailLung, HL: hllung2@hku.hken_HK
dc.identifier.emailChen, H: hlchen@hku.hken_HK
dc.identifier.emailChan, KW: hrmtckw@hku.hken_HK
dc.identifier.emailTsao, SW: gswtsao@hku.hken_HK
dc.identifier.emailChua, DTT: dttchua@hkucc.hku.hken_HK
dc.identifier.emailLung, ML: mlilung@hku.hken_HK
dc.identifier.authorityLung, HL=rp00299en_HK
dc.identifier.authorityChen, H=rp00383en_HK
dc.identifier.authorityChan, KW=rp00330en_HK
dc.identifier.authorityTsao, SW=rp00399en_HK
dc.identifier.authorityChua, DTT=rp00415en_HK
dc.identifier.authorityLung, ML=rp00300en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ijc.25855en_HK
dc.identifier.pmid21165953-
dc.identifier.scopuseid_2-s2.0-80051977695en_HK
dc.identifier.hkuros186355en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-80051977695&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume129en_HK
dc.identifier.issue8en_HK
dc.identifier.spage1826en_HK
dc.identifier.epage1837en_HK
dc.identifier.isiWOS:000294224300004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChan, KC=22633516900en_HK
dc.identifier.scopusauthoridKo, JMY=35725559400en_HK
dc.identifier.scopusauthoridLung, HL=6603819904en_HK
dc.identifier.scopusauthoridSedlacek, R=7005551778en_HK
dc.identifier.scopusauthoridZhang, ZF=50263784500en_HK
dc.identifier.scopusauthoridLuo, DZ=7202658140en_HK
dc.identifier.scopusauthoridFeng, ZB=8429407100en_HK
dc.identifier.scopusauthoridChen, S=36482427400en_HK
dc.identifier.scopusauthoridChen, H=26643315400en_HK
dc.identifier.scopusauthoridChan, KW=16444133100en_HK
dc.identifier.scopusauthoridTsao, SW=7102813116en_HK
dc.identifier.scopusauthoridChua, DTT=7006773480en_HK
dc.identifier.scopusauthoridZabarovsky, ER=7007009108en_HK
dc.identifier.scopusauthoridStanbridge, EJ=7103249410en_HK
dc.identifier.scopusauthoridLung, ML=7006411788en_HK

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