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Article: Genetic and epigenetic inactivation of T-cadherin in human hepatocellular carcinoma cells

TitleGenetic and epigenetic inactivation of T-cadherin in human hepatocellular carcinoma cells
Authors
Keywordsc-Jun
Endothelial cells
HCC
Hepatocellular carcinoma cells
Hypermethylation
LOH
T-cadherin
Underexpression
Issue Date2008
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, 2008, v. 123 n. 5, p. 1043-1052 How to Cite?
AbstractT-cadherin is an atypical cadherin and growing evidence has indicated that T-cadherin exerts tumor-suppressive effects on cancers of epithelial cell type and also causes positive effects on tumor angiogenesis. Human hepatocellular carcinoma (HCC) is a hypervascular tumor and T-cadherin has been shown to be overexpressed in intratumoral endothelial cells of HCCs. However, the expression status and functions of T-cadherin in hepatocytes or HCC cells remain unclear. Here, we demonstrated that T-cadherin was underexpressed in HCC cells (26.5%, 13/49 cases), but was frequently (77.6%, 38/49) overexpressed in intratumoral endothelial cells immunohistochemically. Semiquantitative RT-PCR analysis also showed that the T-cadherin gene was underexpressed in 7 of 11 HCC cell lines. Loss of heterozygosity analysis revealed that 32-38% of the 42 human HCC samples had allelic losses at this locus. Upon pharmacological treatment with demethylating agent 5-aza-2′-deoxycytidine or histone deacetylase inhibitor trichostatin A, T-cadherin promoter hypermethylation and/or histone deacetylation was frequently observed in HCC samples and cell lines. Functionally, enforced expression of T-cadherin induced G2/M cell cycle arrest, reduced cell proliferation in low serum medium, suppressed anchorage-independent growth in soft agar and increased sensitivity to TNFα-mediated apoptosis in HCC cells. Intriguingly, we found that T-cadherin significantly suppressed the activity of c-Jun, a crucial oncoprotein constitutively activated in HCC cells. To conclude, T-cadherin was differentially expressed in human HCCs. The underexpression of T-cadherin in HCC cells suggests it may be another critical event in addition to T-cadherin-mediated angiogenesis during HCC development. © 2006 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/60586
ISSN
2015 Impact Factor: 5.531
2015 SCImago Journal Rankings: 2.657
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, DWen_HK
dc.contributor.authorLee, JMFen_HK
dc.contributor.authorChan, PCYen_HK
dc.contributor.authorNg, IOLen_HK
dc.date.accessioned2010-05-31T04:14:13Z-
dc.date.available2010-05-31T04:14:13Z-
dc.date.issued2008en_HK
dc.identifier.citationInternational Journal Of Cancer, 2008, v. 123 n. 5, p. 1043-1052en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/60586-
dc.description.abstractT-cadherin is an atypical cadherin and growing evidence has indicated that T-cadherin exerts tumor-suppressive effects on cancers of epithelial cell type and also causes positive effects on tumor angiogenesis. Human hepatocellular carcinoma (HCC) is a hypervascular tumor and T-cadherin has been shown to be overexpressed in intratumoral endothelial cells of HCCs. However, the expression status and functions of T-cadherin in hepatocytes or HCC cells remain unclear. Here, we demonstrated that T-cadherin was underexpressed in HCC cells (26.5%, 13/49 cases), but was frequently (77.6%, 38/49) overexpressed in intratumoral endothelial cells immunohistochemically. Semiquantitative RT-PCR analysis also showed that the T-cadherin gene was underexpressed in 7 of 11 HCC cell lines. Loss of heterozygosity analysis revealed that 32-38% of the 42 human HCC samples had allelic losses at this locus. Upon pharmacological treatment with demethylating agent 5-aza-2′-deoxycytidine or histone deacetylase inhibitor trichostatin A, T-cadherin promoter hypermethylation and/or histone deacetylation was frequently observed in HCC samples and cell lines. Functionally, enforced expression of T-cadherin induced G2/M cell cycle arrest, reduced cell proliferation in low serum medium, suppressed anchorage-independent growth in soft agar and increased sensitivity to TNFα-mediated apoptosis in HCC cells. Intriguingly, we found that T-cadherin significantly suppressed the activity of c-Jun, a crucial oncoprotein constitutively activated in HCC cells. To conclude, T-cadherin was differentially expressed in human HCCs. The underexpression of T-cadherin in HCC cells suggests it may be another critical event in addition to T-cadherin-mediated angiogenesis during HCC development. © 2006 Wiley-Liss, Inc.en_HK
dc.languageengen_HK
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.en_HK
dc.subjectc-Junen_HK
dc.subjectEndothelial cellsen_HK
dc.subjectHCCen_HK
dc.subjectHepatocellular carcinoma cellsen_HK
dc.subjectHypermethylationen_HK
dc.subjectLOHen_HK
dc.subjectT-cadherinen_HK
dc.subjectUnderexpressionen_HK
dc.subject.meshAcetylation - drug effectsen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshAnticarcinogenic Agents - metabolismen_HK
dc.subject.meshAntimetabolites, Antineoplastic - pharmacologyen_HK
dc.subject.meshApoptosis - drug effectsen_HK
dc.subject.meshAzacitidine - analogs & derivatives - pharmacologyen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshCadherins - drug effects - genetics - metabolismen_HK
dc.subject.meshCarcinoma, Hepatocellular - drug therapy - genetics - metabolismen_HK
dc.subject.meshCell Cycle - drug effectsen_HK
dc.subject.meshCell Proliferation - drug effectsen_HK
dc.subject.meshDNA Methylation - drug effectsen_HK
dc.subject.meshDNA Modification Methylases - antagonists & inhibitorsen_HK
dc.subject.meshDown-Regulationen_HK
dc.subject.meshEpigenesis, Genetic - drug effectsen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGene Expression Regulation, Neoplastic - drug effectsen_HK
dc.subject.meshGene Silencing - drug effectsen_HK
dc.subject.meshHistone Deacetylase Inhibitorsen_HK
dc.subject.meshHistones - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshHydroxamic Acids - pharmacologyen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshLiver Neoplasms - drug therapy - genetics - metabolismen_HK
dc.subject.meshLoss of Heterozygosityen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshPromoter Regions, Geneticen_HK
dc.subject.meshProto-Oncogene Proteins c-jun - drug effects - metabolismen_HK
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_HK
dc.subject.meshUp-Regulationen_HK
dc.titleGenetic and epigenetic inactivation of T-cadherin in human hepatocellular carcinoma cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=123&spage=1043&epage=1052&date=2008&atitle=Genetic+and+epigenetic+inactivation+of+T-cadherin+in+human+hepatocellular+carcinoma+cellsen_HK
dc.identifier.emailChan, DW:dwchan@hkucc.hku.hken_HK
dc.identifier.emailNg, IOL:iolng@hkucc.hku.hken_HK
dc.identifier.authorityChan, DW=rp00543en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ijc.23634en_HK
dc.identifier.pmid18553387-
dc.identifier.scopuseid_2-s2.0-47249149299en_HK
dc.identifier.hkuros145621en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-47249149299&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume123en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1043en_HK
dc.identifier.epage1052en_HK
dc.identifier.isiWOS:000258243300008-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridChan, DW=26533900600en_HK
dc.identifier.scopusauthoridLee, JMF=36065603500en_HK
dc.identifier.scopusauthoridChan, PCY=24491622600en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK
dc.identifier.citeulike3167977-

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