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Article: HNF1α and CDX2 transcriptional factors bind to cadherin-17 (CDH17) gene promoter and modulate its expression in hepatocellular carcinoma

TitleHNF1α and CDX2 transcriptional factors bind to cadherin-17 (CDH17) gene promoter and modulate its expression in hepatocellular carcinoma
Authors
KeywordsCaudal-Related Homeobox 2
CDH17
Hepatic Nuclear Factor 1α
Hepatocellular Carcinomas
Promoter
Issue Date2010
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35503
Citation
Journal Of Cellular Biochemistry, 2010, v. 111 n. 3, p. 618-626 How to Cite?
AbstractCadherin-17 (CDH17) belongs to the cell adhesion cadherin family with a prominent role in tumorigenesis. It is highly expressed in human hepatocellular carcinoma (HCC) and is proposed to be a biomarker and therapeutic molecule for liver malignancy. The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC. A 1-kb upstream sequence of CDH17 gene was cloned and the promoter activity was studied by luciferase reporter assay. By bioinformatics analysis, deletion and mutation assays, and chromatin immunoprecipitation studies, we identified hepatic nuclear factor 1a (HNF1a) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L). A consistent down-regulation of CDH17 and the two transcriptional activators (HNF1a and CDX2) expression was found in the liver of mouse during development, as well as in human liver cancer cells with less metastatic potential. Suppression of HNF1a and CDX2 expression by small interfering RNA (siRNA) significantly down-regulated expressions of CDH17 and its downstream target cyclin D1 and the viability of HCC cells in vitro. In summary, we identified the minimal promoter region of CDH17 that is regulated by HNF1a and CDX2 transcriptional factors. The present findings enhance our understanding on the regulatory mechanisms of CDH17 oncogene in HCC, and may shed new insights into targeting CDH17 expression as potential therapeutic intervention for cancer treatment. © 2010 Wiley-Liss, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/129379
ISSN
2015 Impact Factor: 3.446
2015 SCImago Journal Rankings: 1.520
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council of Hong KongHKU771607M
Funding Information:

The work is supported by the General Research Fund (HKU771607M) of the Research Grants Council of Hong Kong. The authors thank Dr. Jana Wo for the technical assistance on microscopic surgery of fetal mouse liver, Dr. Arieh Bomzon for critical review, and professional editing of the manuscript.

References

 

DC FieldValueLanguage
dc.contributor.authorZhu, Ren_HK
dc.contributor.authorWong, KFen_HK
dc.contributor.authorLee, NPYen_HK
dc.contributor.authorLee, KFen_HK
dc.contributor.authorLuk, JMCen_HK
dc.date.accessioned2010-12-23T08:36:33Z-
dc.date.available2010-12-23T08:36:33Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Cellular Biochemistry, 2010, v. 111 n. 3, p. 618-626en_HK
dc.identifier.issn0730-2312en_HK
dc.identifier.urihttp://hdl.handle.net/10722/129379-
dc.description.abstractCadherin-17 (CDH17) belongs to the cell adhesion cadherin family with a prominent role in tumorigenesis. It is highly expressed in human hepatocellular carcinoma (HCC) and is proposed to be a biomarker and therapeutic molecule for liver malignancy. The present study aims to identify the transcription factors which interact and regulate CDH17 promoter activity that might contribute to the up-regulation of CDH17 gene in human HCC. A 1-kb upstream sequence of CDH17 gene was cloned and the promoter activity was studied by luciferase reporter assay. By bioinformatics analysis, deletion and mutation assays, and chromatin immunoprecipitation studies, we identified hepatic nuclear factor 1a (HNF1a) and caudal-related homeobox 2 (CDX2) binding sites at the proximal promoter region which modulate the CDH17 promoter activities in two HCC cell lines (Hep3B and MHCC97L). A consistent down-regulation of CDH17 and the two transcriptional activators (HNF1a and CDX2) expression was found in the liver of mouse during development, as well as in human liver cancer cells with less metastatic potential. Suppression of HNF1a and CDX2 expression by small interfering RNA (siRNA) significantly down-regulated expressions of CDH17 and its downstream target cyclin D1 and the viability of HCC cells in vitro. In summary, we identified the minimal promoter region of CDH17 that is regulated by HNF1a and CDX2 transcriptional factors. The present findings enhance our understanding on the regulatory mechanisms of CDH17 oncogene in HCC, and may shed new insights into targeting CDH17 expression as potential therapeutic intervention for cancer treatment. © 2010 Wiley-Liss, Inc.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/35503en_HK
dc.relation.ispartofJournal of Cellular Biochemistryen_HK
dc.rightsThe definitive version is available at www3.interscience.wiley.com-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectCaudal-Related Homeobox 2en_HK
dc.subjectCDH17en_HK
dc.subjectHepatic Nuclear Factor 1αen_HK
dc.subjectHepatocellular Carcinomasen_HK
dc.subjectPromoteren_HK
dc.subject.meshCadherins - genetics-
dc.titleHNF1α and CDX2 transcriptional factors bind to cadherin-17 (CDH17) gene promoter and modulate its expression in hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.emailLee, NPY: nikkilee@hku.hken_HK
dc.identifier.emailLee, KF: ckflee@hku.hken_HK
dc.identifier.emailLuk, JMC: jmluk@hkucc.hku.hken_HK
dc.identifier.authorityLee, NPY=rp00263en_HK
dc.identifier.authorityLee, KF=rp00458en_HK
dc.identifier.authorityLuk, JMC=rp00349en_HK
dc.description.naturepreprint-
dc.identifier.doi10.1002/jcb.22742en_HK
dc.identifier.pmid20568120-
dc.identifier.scopuseid_2-s2.0-78651342510en_HK
dc.identifier.hkuros183300en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78651342510&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume111en_HK
dc.identifier.issue3en_HK
dc.identifier.spage618en_HK
dc.identifier.epage626en_HK
dc.identifier.isiWOS:000282559200011-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridZhu, R=37098459300en_HK
dc.identifier.scopusauthoridWong, KF=35081410800en_HK
dc.identifier.scopusauthoridLee, NPY=7402722690en_HK
dc.identifier.scopusauthoridLee, KF=26643097500en_HK
dc.identifier.scopusauthoridLuk, JMC=7006777791en_HK

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