File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Dickkopf 4 (DKK4) acts on Wnt/β-catenin pathway by influencing β-catenin in hepatocellular carcinoma

TitleDickkopf 4 (DKK4) acts on Wnt/β-catenin pathway by influencing β-catenin in hepatocellular carcinoma
Authors
KeywordsAnimal experiment
Cancer cell culture
Carcinogenicity
Cell assay
Cell growth
Issue Date2012
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/onc
Citation
Oncogene, 2012, v. 31 n. 38, p. 4233-4244 How to Cite?
AbstractDeregulation of Wnt/beta-catenin pathway is a hallmark of major gastrointestinal cancers including hepatocellular carcinoma (HCC). The oncogenic role of beta-catenin is well defined but reasons for its accumulation in HCC remain unclear. Dickkopf 4 (DKK4) acts as a negative regulator of Wnt/beta-catenin pathway but its functional role in liver carcinogenesis has not been studied. We investigated the role of DKK4 in beta-catenin regulation in HCC. Reduced expression of DKK4 was found in 47% (38/81) of HCC, as measured by quantitative real time PCR. Ectopic expression of DKK4 in two HCC cell lines, PLC/PRF/5 (PLC) and MHCC97L (97L), attenuated beta-catenin responsive luciferase activity, and decreased both beta-catenin and cyclin D1 protein levels. To study the effect of DKK4 on cell growth and tumourigenicity, two stable HCC cell lines were established from PLC and 97L cells. Functional assays demonstrated that overexpression of DKK4 hampered cell proliferation, reduced colony formation and retarded cell migration. When DKK4-expressing 97L stable cells were used to induce tumour xenografts in nude mice (n=8), reduction in tumour sizes was observed (P=0.027). Furthermore, immunohistochemical studies showed that decreased expression of DKK4 was associated with beta-catenin accumulation in HCC tissues. Additionally, inhibition of the proteasome using specific inhibitor in DKK4-expressing 97L stable cells masked the effect of beta-catenin. Our findings suggest a potential tumour suppressive role of DKK4 as well as that of an important regulator of HCC.
Persistent Identifierhttp://hdl.handle.net/10722/145952
ISSN
2015 Impact Factor: 7.932
2015 SCImago Journal Rankings: 4.047
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFatima, Sen_HK
dc.contributor.authorLee, NPen_HK
dc.contributor.authorTsang, FHen_HK
dc.contributor.authorKolligs, FTen_HK
dc.contributor.authorNg, IOLen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorFan, STen_HK
dc.contributor.authorLuk, JMen_HK
dc.date.accessioned2012-03-27T09:03:55Z-
dc.date.available2012-03-27T09:03:55Z-
dc.date.issued2012en_HK
dc.identifier.citationOncogene, 2012, v. 31 n. 38, p. 4233-4244en_HK
dc.identifier.issn0950-9232en_HK
dc.identifier.urihttp://hdl.handle.net/10722/145952-
dc.description.abstractDeregulation of Wnt/beta-catenin pathway is a hallmark of major gastrointestinal cancers including hepatocellular carcinoma (HCC). The oncogenic role of beta-catenin is well defined but reasons for its accumulation in HCC remain unclear. Dickkopf 4 (DKK4) acts as a negative regulator of Wnt/beta-catenin pathway but its functional role in liver carcinogenesis has not been studied. We investigated the role of DKK4 in beta-catenin regulation in HCC. Reduced expression of DKK4 was found in 47% (38/81) of HCC, as measured by quantitative real time PCR. Ectopic expression of DKK4 in two HCC cell lines, PLC/PRF/5 (PLC) and MHCC97L (97L), attenuated beta-catenin responsive luciferase activity, and decreased both beta-catenin and cyclin D1 protein levels. To study the effect of DKK4 on cell growth and tumourigenicity, two stable HCC cell lines were established from PLC and 97L cells. Functional assays demonstrated that overexpression of DKK4 hampered cell proliferation, reduced colony formation and retarded cell migration. When DKK4-expressing 97L stable cells were used to induce tumour xenografts in nude mice (n=8), reduction in tumour sizes was observed (P=0.027). Furthermore, immunohistochemical studies showed that decreased expression of DKK4 was associated with beta-catenin accumulation in HCC tissues. Additionally, inhibition of the proteasome using specific inhibitor in DKK4-expressing 97L stable cells masked the effect of beta-catenin. Our findings suggest a potential tumour suppressive role of DKK4 as well as that of an important regulator of HCC.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/oncen_HK
dc.relation.ispartofOncogeneen_HK
dc.subjectAnimal experiment-
dc.subjectCancer cell culture-
dc.subjectCarcinogenicity-
dc.subjectCell assay-
dc.subjectCell growth-
dc.titleDickkopf 4 (DKK4) acts on Wnt/β-catenin pathway by influencing β-catenin in hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0950-9232&volume=Epub on 2012-01-16&spage=&epage=&date=2012&atitle=Dickkopf+4+(DKK4)+acts+on+Wnt/β-catenin+pathway+by+influencing+β-catenin+in+hepatocellular+carcinomaen_US
dc.identifier.emailFatima, S: sarwat@hkucc.hku.hken_HK
dc.identifier.emailLee, NP: nikkilee@hku.hken_HK
dc.identifier.emailNg, IOL: iolng@hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.emailLuk, JM: jmluk@hkucc.hku.hk-
dc.identifier.authorityLee, NP=rp00263en_HK
dc.identifier.authorityNg, IOL=rp00335en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.identifier.authorityLuk, JM=rp00349en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/onc.2011.580en_HK
dc.identifier.pmid22249261-
dc.identifier.scopuseid_2-s2.0-84866549389en_HK
dc.identifier.hkuros198963en_US
dc.identifier.volume31en_US
dc.identifier.issue38-
dc.identifier.spage4233-
dc.identifier.epage4244-
dc.identifier.eissn1476-5594-
dc.identifier.isiWOS:000308975800006-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLuk, JM=7006777791en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridNg, IOL=7102753722en_HK
dc.identifier.scopusauthoridKolligs, FT=6602736110en_HK
dc.identifier.scopusauthoridTsang, FH=36895782100en_HK
dc.identifier.scopusauthoridLee, NP=7402722690en_HK
dc.identifier.scopusauthoridFatima, S=8437472300en_HK

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats