Characterization of FAM134B in the context of hepatocellular carcinoma and endoplasmic reticulum protein stress

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buir.advisorÖztürk, Mehmet
dc.contributor.authorYılmaz, Mustafa
dc.date.accessioned2016-01-08T18:23:45Z
dc.date.available2016-01-08T18:23:45Z
dc.date.issued2011
dc.descriptionAnkara : The Department of Molecular Biology and Genetics and Graduate School of Engineering and Science of Bilkent University, 2011.en_US
dc.descriptionThesis (Master's) -- Bilkent University, 2011.en_US
dc.descriptionIncludes bibliographical refences.en_US
dc.description.abstractFamily with sequence similarity 134, member B (FAM134B) is a replicative senescence associated gene, previously identified in studies of our group as a result of microarray analysis in spontaneously senescent clones of Huh7 hepatocellular carcinoma cell line and their immortal counterparts. Originating from this finding, this study primarily focused on characterization of FAM134B in the context of hepatocellular carcinoma and endoplasmic reticulum stress. At the beginning, the relationship between senescence and FAM134B was experimented by inducing premature senescence in Huh7 cells. Adriamycin or TGF-β induced premature senescence did not result in amplification of FAM134B gene expression, suggesting that upregulation of FAM134B expression in spontaneous replicative senescence is not directly associated with a senescence phenotype. Then, FAM134B mRNA and protein levels were analyzed in both well- and poorly-differentiated HCC cell lines. Results showed that FAM134B expression is greater in poorly-differentiated cell lines, which represent advanced and metastatic HCC in vitro. On the other hand, our studies on the relationship between FAM134B and endoplasmic reticulum (ER) stress showed that FAM134B is an ER stress response gene, whose expression is upregulated by induction of ER stress with chemicals, such as thapsigargin, tunicamycin or DTT. Therefore, high protein and mRNA levels of FAM134B in poorly-differentiated cell lines are linked to the presence of a basal level ER stress response in this group of cell lines. Furthermore, overexpression studies in Huh7 cells indicated that FAM134B cannot trigger an ER stress response or autophagic response in these cells. However, FAM134B was detected as an effector in cellular response, when ER stress is artificially induced by thapsigargin or tunicamycin treatments. FAM13B4 overexpression in Huh7 resulted in increased sensitivity to thapsigargin or tunicamycin induced apoptosis. Moreover, increased FAM134B expression was also associated with decreased proliferative capacity in response to ER stress induction with the same chemicals. Consequently, FAM134B was suggested to affect the severity of stress in the ER when ER stress is started with an inducer. In addition, our tissue based experiments revealed that FAM134B is expressed in the brain and liver. Taken together, FAM134B might be an important protein contributing to the liver tissue damage and pathogenesis of HCC.en_US
dc.description.provenanceMade available in DSpace on 2016-01-08T18:23:45Z (GMT). No. of bitstreams: 1 0006440.pdf: 2705646 bytes, checksum: 70d7d663c4d9b0c62e64d4ab730b8a34 (MD5)en
dc.description.statementofresponsibilityYılmaz, Mustafaen_US
dc.format.extentxvii, 98 leaves, illustrations, graphsen_US
dc.identifier.urihttp://hdl.handle.net/11693/15728
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject.lccWI735 .Y55 2011en_US
dc.subject.lcshCarcinoma, Hepatocellular.en_US
dc.subject.lcshCancer--Genetic aspects.en_US
dc.subject.lcshDNA-Protein interaction.en_US
dc.subject.lcshProtein interaction.en_US
dc.subject.lcshCancer cells.en_US
dc.subject.lcshp53 antioncogene.en_US
dc.subject.lcshLiver cancer.en_US
dc.subject.lcshEndoplasmic reticulum.en_US
dc.subject.lcshCarcinogenesis.en_US
dc.titleCharacterization of FAM134B in the context of hepatocellular carcinoma and endoplasmic reticulum protein stressen_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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