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Article: Characterization of a candidate tumor suppressor gene uroplakin 1A in esophageal squamous cell carcinoma

TitleCharacterization of a candidate tumor suppressor gene uroplakin 1A in esophageal squamous cell carcinoma
Authors
Issue Date2010
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
Cancer Research, 2010, v. 70 n. 21, p. 8832-8841 How to Cite?
AbstractEsophageal squamous cell carcinoma (ESCC) is increasing in incidence, but the knowledge of the genetic underpinnings of this disease remains limited. In this study, we identified the tetraspanin cell surface receptor uroplakin 1A (UPK1A) as a candidate tumor suppressor gene (TSG), and we investigated its function and mechanism in ESCC cells. UPK1A downregulation occurred in 68% of primary ESCCs examined, where it was correlated significantly with promoter hypermethylation (P < 0.05). Ectopic expression of UPK1A in ESCC cells inhibited cell proliferation, clonogenicity, cell motility, and tumor formation in nude mice. Mechanistic investigations suggested that these effects may be mediated by inhibiting nuclear translocation of β-catenin and inactivation of its downstream targets, including cyclin-D1, c-jun, c-myc, and matrix metalloproteinase 7 (MMP7). Cell cycle arrest elicited by UPK1A at the G 1-S checkpoint was associated with downregulation of cyclin D1 and cyclin-dependent kinase 4, whereas metastasis suppression was associated with reduction of MMP7. These findings were consistent with evidence derived from clinical samples, where UPK1A downregulation was correlated with lymph node metastasis (P = 0.009), stage (P = 0.015), and overall survival (P < 0.0001). Indeed, multivariate cyclooxygenase regression analysis showed that UPK1A was an independent prognostic factor for overall survival. Taken together, our findings define a function for UPK1A as an important TSG in ESCC development. ©2010 AACR.
Persistent Identifierhttp://hdl.handle.net/10722/148753
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grant CouncilHKU 1/06C
Sun Yat-Sen University85000-3171311
Major State Basic Research Program of China2006CB910104
HKU7393/04M
Funding Information:

Research Council grant HKU 7393/04M, Hong Kong Research Grant Council Central Allocation grant HKU 1/06C, Sun Yat-Sen University "Hundred Talents Program" grant 85000-3171311, and Major State Basic Research Program of China grant 2006CB910104.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorKong, KLen_HK
dc.contributor.authorKwong, DLen_HK
dc.contributor.authorFu, Len_HK
dc.contributor.authorChan, THMen_HK
dc.contributor.authorChen, Len_HK
dc.contributor.authorLiu, Hen_HK
dc.contributor.authorLi, Yen_HK
dc.contributor.authorZhu, YHen_HK
dc.contributor.authorBi, Jen_HK
dc.contributor.authorQin, YRen_HK
dc.contributor.authorLaw, SYKen_HK
dc.contributor.authorGuan, XYen_HK
dc.date.accessioned2012-06-06T05:36:11Z-
dc.date.available2012-06-06T05:36:11Z-
dc.date.issued2010en_HK
dc.identifier.citationCancer Research, 2010, v. 70 n. 21, p. 8832-8841en_HK
dc.identifier.issn0008-5472en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148753-
dc.description.abstractEsophageal squamous cell carcinoma (ESCC) is increasing in incidence, but the knowledge of the genetic underpinnings of this disease remains limited. In this study, we identified the tetraspanin cell surface receptor uroplakin 1A (UPK1A) as a candidate tumor suppressor gene (TSG), and we investigated its function and mechanism in ESCC cells. UPK1A downregulation occurred in 68% of primary ESCCs examined, where it was correlated significantly with promoter hypermethylation (P < 0.05). Ectopic expression of UPK1A in ESCC cells inhibited cell proliferation, clonogenicity, cell motility, and tumor formation in nude mice. Mechanistic investigations suggested that these effects may be mediated by inhibiting nuclear translocation of β-catenin and inactivation of its downstream targets, including cyclin-D1, c-jun, c-myc, and matrix metalloproteinase 7 (MMP7). Cell cycle arrest elicited by UPK1A at the G 1-S checkpoint was associated with downregulation of cyclin D1 and cyclin-dependent kinase 4, whereas metastasis suppression was associated with reduction of MMP7. These findings were consistent with evidence derived from clinical samples, where UPK1A downregulation was correlated with lymph node metastasis (P = 0.009), stage (P = 0.015), and overall survival (P < 0.0001). Indeed, multivariate cyclooxygenase regression analysis showed that UPK1A was an independent prognostic factor for overall survival. Taken together, our findings define a function for UPK1A as an important TSG in ESCC development. ©2010 AACR.en_HK
dc.languageengen_US
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/en_HK
dc.relation.ispartofCancer Researchen_HK
dc.subject.meshAnimalsen_US
dc.subject.meshApoptosisen_US
dc.subject.meshBlotting, Westernen_US
dc.subject.meshCarcinoma, Squamous Cell - Genetics - Metabolism - Pathologyen_US
dc.subject.meshCell Adhesionen_US
dc.subject.meshCell Movementen_US
dc.subject.meshCell Proliferationen_US
dc.subject.meshDna Methylationen_US
dc.subject.meshEsophageal Neoplasms - Genetics - Metabolism - Pathologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshFluorescent Antibody Techniqueen_US
dc.subject.meshGenes, Tumor Suppressor - Physiologyen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoenzyme Techniquesen_US
dc.subject.meshLiver Neoplasms - Genetics - Metabolism - Secondaryen_US
dc.subject.meshLung Neoplasms - Genetics - Metabolism - Secondaryen_US
dc.subject.meshLymphatic Metastasisen_US
dc.subject.meshMaleen_US
dc.subject.meshMembrane Glycoproteins - Genetics - Metabolismen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Sciden_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshRna, Messenger - Geneticsen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshTissue Array Analysisen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.subject.meshUroplakin Iaen_US
dc.subject.meshWound Healingen_US
dc.subject.meshXenograft Model Antitumor Assaysen_US
dc.titleCharacterization of a candidate tumor suppressor gene uroplakin 1A in esophageal squamous cell carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.emailKwong, DL: dlwkwong@hku.hken_HK
dc.identifier.emailFu, L: gracelfu@hku.hken_HK
dc.identifier.emailLaw, SYK: slaw@hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.authorityKwong, DL=rp00414en_HK
dc.identifier.authorityFu, L=rp01435en_HK
dc.identifier.authorityLaw, SYK=rp00437en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1158/0008-5472.CAN-10-0779en_HK
dc.identifier.pmid20978196-
dc.identifier.scopuseid_2-s2.0-78449296221en_HK
dc.identifier.hkuros183813-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78449296221&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume70en_HK
dc.identifier.issue21en_HK
dc.identifier.spage8832en_HK
dc.identifier.epage8841en_HK
dc.identifier.eissn1538-7445-
dc.identifier.isiWOS:000283667300060-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectMolecular pathology of liver cancer - a multidisciplinary study-
dc.identifier.scopusauthoridKong, KL=36106004300en_HK
dc.identifier.scopusauthoridKwong, DL=15744231600en_HK
dc.identifier.scopusauthoridFu, L=22979236700en_HK
dc.identifier.scopusauthoridChan, THM=26431726400en_HK
dc.identifier.scopusauthoridChen, L=23569135400en_HK
dc.identifier.scopusauthoridLiu, H=34877073600en_HK
dc.identifier.scopusauthoridLi, Y=36078298200en_HK
dc.identifier.scopusauthoridZhu, YH=19338197800en_HK
dc.identifier.scopusauthoridBi, J=7103093361en_HK
dc.identifier.scopusauthoridQin, YR=7403100680en_HK
dc.identifier.scopusauthoridLaw, SYK=7202241293en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK

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