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dc.contributor.advisorÇetin-Atalay, Rengül
dc.contributor.authorÇevik, Dilek
dc.date.accessioned2016-04-22T10:48:52Z
dc.date.available2016-04-22T10:48:52Z
dc.date.copyright2014-09
dc.date.issued2014-09
dc.date.submitted22-10-2014
dc.identifier.urihttp://hdl.handle.net/11693/28969
dc.descriptionCataloged from PDF version of thesis.en_US
dc.descriptionIncludes bibliographical references (leaves 89-112).en_US
dc.descriptionThesis (Ph. D.): Bilkent University, Department of Molecular Biology and Genetics, İhsan Doğramacı Bilkent University, 2014.en_US
dc.description.abstractHepatocellular Carcinoma (HCC) is one of the major causes of cancer related deaths worldwide and its incidence has been increasing drastically, especially in western countries. HCC has a heterogeneous molecular and pathological background with various underlying risk factors and survival rate of HCC patients is very low due to late diagnosis and limited curative therapies. The mechanisms involved in hepatocellular immortality gains critical importance in order to develop preventive and therapeutic options against HCC. Telomerase reactivation is a keystone for HCC cells during transformation process. TERT promoter mutations activating its promoter by creating a novel activating motif were recently identified in different cancer types. In this study; we determined TERT promoter mutation frequency in HCC cell lines and tumors which are 67% (10/15) and 34% (15/44) respectively. High frequency of TERT promoter mutations in HCC indicated a possible functional role during hepatocarcinogenesis. We performed transcriptional factor search to find a candidate TF that could bind to mutant TERT promoter and STAT1 came out of that search. To study the role of STAT1 during reactivation of TERT expression, we activated STAT1 signaling by Interferon alpha (IFN-α) treatment and down regulated STAT1 with RNA interference in several HCC cell lines. We have found that IFN-α was able to upregulate TERT expression in the HCC cell lines carrying a TERT promoter mutation and STAT1 knockdown was enough to eradicate this upregulation. In case of wild type cell lines, IFN-α treatment and STAT1 knock down had no effect on TERT expression. Our data delineates the contributions of TERT promoter mutations to hepatocellular immortality and gives insights into the potential use of TERT as a target for chemoprevention of hepatocarcinogenesis.en_US
dc.description.statementofresponsibilityby Dilek Çevik.en_US
dc.format.extentxvii, 119 leaves : graphics, tables.en_US
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectHepatocellular carcinomaen_US
dc.subjectTERTen_US
dc.subjectPromoter mutationsen_US
dc.subjectSTAT1en_US
dc.subjectInterferon alphaen_US
dc.subjectIFN-αen_US
dc.titleReactivation of telomerase reverse transcriptase gene in liver canceren_US
dc.title.alternativeKaraciğer kanserinde telomeraz revers transkriptaz geninin reaktivasyonuen_US
dc.typeThesisen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.publisherBilkent Universityen_US
dc.description.degreePh.D.en_US
dc.identifier.itemidB148846
dc.embargo.release2016-10-22


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