Genetic analysis of Smad4 gene in TGF-Beta signalling pathway in human liver cancer

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buir.advisorYakıcıer, Cengiz
dc.contributor.authorIrmak, Meliha Burcu
dc.date.accessioned2016-01-08T20:15:42Z
dc.date.available2016-01-08T20:15:42Z
dc.date.issued1998
dc.descriptionAnkara : The Department of Molecular Biology and Genetics and Institute of Engineering and Science, Bilkent Univ., 1998.en_US
dc.descriptionThesis (Master's) -- Bilkent University, 1998.en_US
dc.descriptionIncludes bibliographical references leaves 49-57.en_US
dc.description.abstractHCC is a multistep genetic disease in which many genomic changes occur as a result of uncontrolled proliferation of hepatocytes. Molecular events leading to HCC is still unclear. Until now, neither an oncogene nor a tumor suppressor gene has been shown to be prefentially altered in HCC. Genetic alterations other than p53, pl6, BRCA2 (Breast Carcinoma Associated Protein), M6P/IGFIIR (lyiannose 6 Phosphate/ Insulin Like Growth Factor II Receptor), Rb (Retinoblastoma), PRLTS (Platelet Derived Growth Factor Receptor-|3-Like Tumor Suppressor Gene), and Tg737 (Candidate polycyctic kidney disease gene) genes remain unknown. TGF-P is a strong inhibitor of hepatocyte proliferation. In HCC and cirrhosis increased levels of TGF-P is observed, so this shows that the presence of high levels of TGF-3 does not avoid hepatocyte proliferation. Thus, there may be a disruption in the signalling pathway of TGF-p. The common mediator Smad4 gene, which is among the genes located in TGF-P signalling pathway, is found to be mutated in many cancer types. We decided to do the mutational analysis of Smad4 gene, which is located in the signalling pathway of the hepatocyte antiproliferative factor, TGF-p. Exons 8, 9, 10, and 11 which are in MH2 region, and exon 2 which is in MHl region of Smad4 is mutationally analysed by SSCP for 35 HCC cases. In the 35 HCC tumors, 5 alterations were observed (14%), 3 of them being in exon 8, one of them being in exon 9a, and the last one being in exon 10 of Smad4 gene. In the samples we tested, no big deletions were observed, but the alterations observed are probably single base changes. Also HCC cell lines namely, HepG2, Hep3B, Huh-7, FOCUS, Mahlavu, and PLC/PRF/5 were checked for their mutations and cell lines other then PLC/PRF/5 were analysed for their mRNA transcription. There were no big deletions or alterations in Nand C- terminals of the cell lines and we have shown mRNA transcription for all cell lines except Hep3B in which PCR has revealed very weak amplification. Our results suggest that Smad4 might be involved in at least a part of primary HCC tumor development.en_US
dc.description.provenanceMade available in DSpace on 2016-01-08T20:15:42Z (GMT). No. of bitstreams: 1 1.pdf: 78510 bytes, checksum: d85492f20c2362aa2bcf4aad49380397 (MD5)en
dc.description.statementofresponsibilityIrmak, Meliha Burcuen_US
dc.format.extentxii, 57 leaves, illustrationsen_US
dc.identifier.urihttp://hdl.handle.net/11693/18042
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectHCCen_US
dc.subjectTGF-3en_US
dc.subjectMutationen_US
dc.subjectSmad4en_US
dc.subjectCell lineen_US
dc.subjectSSCPen_US
dc.subjectPCRen_US
dc.subject.lccWI735 .I74 1998en_US
dc.subject.lcshLiver--Cancer.en_US
dc.subject.lcshCarcinogenesis.en_US
dc.subject.lcshLiver cells.en_US
dc.subject.lcshCarcinoma.en_US
dc.subject.lcshHepatitis viruses.en_US
dc.subject.lcshLiver neoplasms.en_US
dc.subject.lcshLiver--Molecular aspects.en_US
dc.subject.lcshPathology, Molecular.en_US
dc.titleGenetic analysis of Smad4 gene in TGF-Beta signalling pathway in human liver canceren_US
dc.typeThesisen_US
thesis.degree.disciplineMolecular Biology and Genetics
thesis.degree.grantorBilkent University
thesis.degree.levelMaster's
thesis.degree.nameMS (Master of Science)

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