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Article: Deleted in liver cancer 1 isoforms are distinctly expressed in human tissues, functionally different and under differential transcriptional regulation in hepatocellular carcinoma

TitleDeleted in liver cancer 1 isoforms are distinctly expressed in human tissues, functionally different and under differential transcriptional regulation in hepatocellular carcinoma
Authors
KeywordsDeleted in liver cancer 1
Hepatocellular carcinoma
Isoforms
Issue Date2010
PublisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1478-3223&site=1
Citation
Liver International, 2010, v. 30 n. 1, p. 139-148 How to Cite?
AbstractBackground: Deleted in liver cancer (DLC) is a family of tumour suppressors that plays a critical role in hepatocellular carcinoma (HCC). Aims: This study aimed to document the expression profiles of the three known DLC1 isoforms (α, β and γ) in normal human tissues and human HCCs and address their functional and regulatory differences. We also aimed to determine the clinicopathological and prognostic significance of the DLC1 dominant isoform in human HCCs. Methods: Quantitative polymerase chain reaction was performed to determine the expressions of DLC1 isoforms in different normal human tissues and human HCCs. The clinicopathological and prognostic significance of DLC1 expression in HCC samples was also analysed. In addition, the functional roles of DLC1 isoforms were addressed using HCC cell lines to examine their abilities to suppress stress fibre formation and HCC cell growth. Results: DLC1α was the most predominant of the three isoforms in the normal human tissues examined, except the heart. The DLC1α promoter, but not the DLC1β and γ promoter, was hypermethylated and epigenetically silenced in HCC cells. Underexpression of DLC1α at the mRNA level was frequently (52.5%, n = 52) observed in the 99 HCCs as compared with the corresponding nontumorous liver tissues. DLC1α underexpression correlated with poorer tumour cellular differentiation (P = 0.010). Functionally, DLC1α and β, but not DLC1γ, were localized at focal adhesions of cells and able to inhibit stress fibre formation and suppress HCC cell growth. Conclusions: The results suggested that DLC1 isoforms are differentially expressed in human tissues, have different epigenetic transcriptional regulations and are functionally different. DLC1α was underexpressed and clinically relevant in human HCCs. © 2009 John Wiley & Sons A/S.
Persistent Identifierhttp://hdl.handle.net/10722/88501
ISSN
2015 Impact Factor: 4.47
2015 SCImago Journal Rankings: 1.677
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU7798/07M
RGC Collaborative Research GrantsHKU 1/06C
University of Hong Kong Seed Funding Programme for Basic Research2008-2010
SRT Seed Funding2005-2007
Funding Information:

This study was supported by the Hong Kong Research Grants Council (HKU7798/07M), RGC Collaborative Research Grants (HKU 1/06C), the University of Hong Kong Seed Funding Programme for Basic Research 2008-2010 and SRT Seed Funding 2005-2007. I. O. L. Ng is Loke Yew Professor in Pathology.

References
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DC FieldValueLanguage
dc.contributor.authorKo, FCFen_HK
dc.contributor.authorYeung, YSen_HK
dc.contributor.authorWong, CMen_HK
dc.contributor.authorChan, LKen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorNg, IOLen_HK
dc.contributor.authorYam, JWPen_HK
dc.date.accessioned2010-09-06T09:44:11Z-
dc.date.available2010-09-06T09:44:11Z-
dc.date.issued2010en_HK
dc.identifier.citationLiver International, 2010, v. 30 n. 1, p. 139-148en_HK
dc.identifier.issn1478-3223en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88501-
dc.description.abstractBackground: Deleted in liver cancer (DLC) is a family of tumour suppressors that plays a critical role in hepatocellular carcinoma (HCC). Aims: This study aimed to document the expression profiles of the three known DLC1 isoforms (α, β and γ) in normal human tissues and human HCCs and address their functional and regulatory differences. We also aimed to determine the clinicopathological and prognostic significance of the DLC1 dominant isoform in human HCCs. Methods: Quantitative polymerase chain reaction was performed to determine the expressions of DLC1 isoforms in different normal human tissues and human HCCs. The clinicopathological and prognostic significance of DLC1 expression in HCC samples was also analysed. In addition, the functional roles of DLC1 isoforms were addressed using HCC cell lines to examine their abilities to suppress stress fibre formation and HCC cell growth. Results: DLC1α was the most predominant of the three isoforms in the normal human tissues examined, except the heart. The DLC1α promoter, but not the DLC1β and γ promoter, was hypermethylated and epigenetically silenced in HCC cells. Underexpression of DLC1α at the mRNA level was frequently (52.5%, n = 52) observed in the 99 HCCs as compared with the corresponding nontumorous liver tissues. DLC1α underexpression correlated with poorer tumour cellular differentiation (P = 0.010). Functionally, DLC1α and β, but not DLC1γ, were localized at focal adhesions of cells and able to inhibit stress fibre formation and suppress HCC cell growth. Conclusions: The results suggested that DLC1 isoforms are differentially expressed in human tissues, have different epigenetic transcriptional regulations and are functionally different. DLC1α was underexpressed and clinically relevant in human HCCs. © 2009 John Wiley & Sons A/S.en_HK
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing, Inc.. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1478-3223&site=1en_HK
dc.relation.ispartofLiver Internationalen_HK
dc.subjectDeleted in liver cancer 1en_HK
dc.subjectHepatocellular carcinomaen_HK
dc.subjectIsoformsen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAgeden_HK
dc.subject.meshAged, 80 and overen_HK
dc.subject.meshCarcinoma, Hepatocellular - genetics - metabolism - pathologyen_HK
dc.subject.meshCell Line, Tumoren_HK
dc.subject.meshEpigenesis, Geneticen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGTPase-Activating Proteinsen_HK
dc.subject.meshGene Expression Regulation, Neoplastic - geneticsen_HK
dc.subject.meshHumansen_HK
dc.subject.meshLiver Neoplasms - genetics - metabolism - pathologyen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshPrognosisen_HK
dc.subject.meshProtein Isoformsen_HK
dc.subject.meshRNA, Messenger - metabolismen_HK
dc.subject.meshTranscription, Geneticen_HK
dc.subject.meshTumor Stem Cell Assayen_HK
dc.subject.meshTumor Suppressor Proteins - genetics - metabolismen_HK
dc.subject.meshYoung Adulten_HK
dc.titleDeleted in liver cancer 1 isoforms are distinctly expressed in human tissues, functionally different and under differential transcriptional regulation in hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1478-3223&volume=30&spage=139&epage=148&date=2010&atitle=Deleted+in+liver+cancer+1+isoforms+are+distinctly+expressed+in+human+tissues,+functionally+different+and+under+differential+transcriptional+regulation+in+hepatocellular+carcinomaen_HK
dc.identifier.emailWong, CM: jackwong@pathology.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.emailNg, IOL: iolng@hkucc.hku.hken_HK
dc.identifier.emailYam, JWP: judyyam@pathology.hku.hken_HK
dc.identifier.authorityWong, CM=rp00231en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.identifier.authorityYam, JWP=rp00468en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1478-3231.2009.02133.xen_HK
dc.identifier.pmid19874489-
dc.identifier.scopuseid_2-s2.0-73349090904en_HK
dc.identifier.hkuros168288en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-73349090904&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume30en_HK
dc.identifier.issue1en_HK
dc.identifier.spage139en_HK
dc.identifier.epage148en_HK
dc.identifier.isiWOS:000272443700017-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectMolecular pathology of liver cancer - a multidisciplinary study-
dc.identifier.scopusauthoridKo, FCF=14630572500en_HK
dc.identifier.scopusauthoridYeung, YS=9841205900en_HK
dc.identifier.scopusauthoridWong, CM=16314668400en_HK
dc.identifier.scopusauthoridChan, LK=24833005000en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK
dc.identifier.scopusauthoridYam, JWP=6603711123en_HK
dc.identifier.citeulike6335408-

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