Show simple item record

dc.contributor.authorAcun, T.en_US
dc.contributor.authorOztas, E.en_US
dc.contributor.authorYagci, T.en_US
dc.contributor.authorYakicier, M.C.en_US
dc.date.accessioned2016-02-08T09:52:39Z
dc.date.available2016-02-08T09:52:39Z
dc.date.issued2011en_US
dc.identifier.issn14712407
dc.identifier.urihttp://hdl.handle.net/11693/21891
dc.description.abstractBackground: Smad interacting protein-1 is a transcription factor that is implicated in transforming growth factor-β/bone morphogenetic protein signaling and a repressor of E-cadherin and human telomerase reverse transcriptase. It is also involved in epithelial-mesenchymal transition and tumorigenesis. However, genetic and epigenetic alterations of SIP1 have not been fully elucidated in cancers. In this study, we investigated mutations and promoter hypermethylation of the SIP1 gene in human hepatocellular carcinomas.Methods: SIP1 expression was analyzed in HCC cell lines and primary tumors in comparison to normal and non-tumor liver tissues by using semi-quantitative RT-PCR, quantitative real-time RT-PCR and immunohistochemistry. Mutation and deletion screening of the SIP1 gene were performed by direct sequencing in HCC-derived cells. Restoration of SIP1 expression was sought by treating HCC cell lines with the DNA methyl transferase inhibitor, 5-AzaC, and the histone deacetylase inhibitor, TSA. SIP1 promoter methylation was analyzed by the combined bisulfite restriction analysis assay in in silico-predicted putative promoter and CpG island regions.Results: We found that the expression of SIP1 was completely lost or reduced in five of 14 (36%) HCC cell lines and 17 of 23 (74%) primary HCC tumors. Immunohistochemical analysis confirmed that SIP1 mRNA downregulation was associated with decreased expression of the SIP1 protein in HCC tissues (82.8%). No somatic mutation was observed in SIP1 exons in any of the 14 HCC cell lines. Combined treatment with DNA methyl transferase and histone deacetylase inhibitors synergistically restored SIP1 expression in SIP1-negative cell lines. Analysis of three putative gene regulatory regions revealed tumor-specific methylation in more than half of the HCC cases.Conclusions: Epigenetic mechanisms contribute significantly to the downregulation of SIP1 expression in HCC. This finding adds a new level of complexity to the role of SIP1 in hepatocarcinogenesis. © 2011 Acun et al; licensee BioMed Central Ltd.en_US
dc.language.isoEnglishen_US
dc.source.titleBMC Canceren_US
dc.relation.isversionofhttp://dx.doi.org/10.1186/1471-2407-11-223en_US
dc.subjectazacitidineen_US
dc.subjectbisulfiteen_US
dc.subjectDNA methyltransferase inhibitoren_US
dc.subjecthistone deacetylase inhibitoren_US
dc.subjectmessenger RNAen_US
dc.subjectSmad interacting protein 1en_US
dc.subjecttranscription factoren_US
dc.subjecttrichostatin Aen_US
dc.subjectunclassified drugen_US
dc.subjectDNA methyltransferaseen_US
dc.subjecthistone deacetylase inhibitoren_US
dc.subjecthomeodomain proteinen_US
dc.subjecthydroxamic aciden_US
dc.subjectrepressor proteinen_US
dc.subjecttrichostatin Aen_US
dc.subjectZEB2 protein, humanen_US
dc.subjectarticleen_US
dc.subjectcancer cell cultureen_US
dc.subjectcancer tissueen_US
dc.subjectcomputer modelen_US
dc.subjectcontrolled studyen_US
dc.subjectCpG islanden_US
dc.subjectDNA methylationen_US
dc.subjectdown regulationen_US
dc.subjectdrug potentiationen_US
dc.subjectepigeneticsen_US
dc.subjectexonen_US
dc.subjectgene deletionen_US
dc.subjectgene mutationen_US
dc.subjectgene sequenceen_US
dc.subjecthumanen_US
dc.subjecthuman tissueen_US
dc.subjectimmunohistochemistryen_US
dc.subjectliveren_US
dc.subjectliver carcinogenesisen_US
dc.subjectliver cell carcinomaen_US
dc.subjectmajor clinical studyen_US
dc.subjectprimary tumoren_US
dc.subjectpromoter regionen_US
dc.subjectprotein expressionen_US
dc.subjectrestriction mappingen_US
dc.subjectreverse transcription polymerase chain reactionen_US
dc.subjectsomatic mutationen_US
dc.subjectadulten_US
dc.subjectageden_US
dc.subjectdown regulationen_US
dc.subjectdrug antagonismen_US
dc.subjectdrug effecten_US
dc.subjectfemaleen_US
dc.subjectgene expression regulationen_US
dc.subjectgenetic transcriptionen_US
dc.subjectgeneticsen_US
dc.subjectliver cell carcinomaen_US
dc.subjectliver tumoren_US
dc.subjectmaleen_US
dc.subjectmetabolismen_US
dc.subjectmiddle ageden_US
dc.subjectmolecular geneticsen_US
dc.subjectnucleotide sequenceen_US
dc.subjectpathologyen_US
dc.subjectpromoter regionen_US
dc.subjecttumor cell lineen_US
dc.subjectAdulten_US
dc.subjectAgeden_US
dc.subjectAged, 80 and overen_US
dc.subjectAzacitidineen_US
dc.subjectBase Sequenceen_US
dc.subjectCarcinoma, Hepatocellularen_US
dc.subjectCell Line, Tumoren_US
dc.subjectDNA Methylationen_US
dc.subjectDNA Modification Methylasesen_US
dc.subjectDNA Mutational Analysisen_US
dc.subjectDown-Regulationen_US
dc.subjectFemaleen_US
dc.subjectGene Expression Regulation, Neoplasticen_US
dc.subjectHistone Deacetylase Inhibitorsen_US
dc.subjectHomeodomain Proteinsen_US
dc.subjectHumansen_US
dc.subjectHydroxamic Acidsen_US
dc.subjectLiver Neoplasmsen_US
dc.subjectMaleen_US
dc.subjectMiddle Ageden_US
dc.subjectMolecular Sequence Dataen_US
dc.subjectPromoter Regions, Geneticen_US
dc.subjectRepressor Proteinsen_US
dc.subjectRestriction Mappingen_US
dc.subjectTranscription, Geneticen_US
dc.subjectYoung Adulten_US
dc.titleSIP1 is downregulated in hepatocellular carcinoma by promoter hypermethylationen_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Genetics
dc.citation.volumeNumber11en_US
dc.identifier.doi10.1186/1471-2407-11-223en_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record