dc.contributor.advisor | Öztürk, Mehmet | |
dc.contributor.author | Yılmaz, Mustafa | |
dc.date.accessioned | 2016-01-08T18:23:45Z | |
dc.date.available | 2016-01-08T18:23:45Z | |
dc.date.issued | 2011 | |
dc.identifier.uri | http://hdl.handle.net/11693/15728 | |
dc.description | Ankara : The Department of Molecular Biology and Genetics and Graduate School of Engineering and Science of Bilkent University, 2011. | en_US |
dc.description | Thesis (Master's) -- Bilkent University, 2011. | en_US |
dc.description | Includes bibliographical refences. | en_US |
dc.description.abstract | Family 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.statementofresponsibility | Yılmaz, Mustafa | en_US |
dc.format.extent | xvii, 98 leaves, illustrations, graphs | en_US |
dc.language.iso | English | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject.lcc | WI735 .Y55 2011 | en_US |
dc.subject.lcsh | Carcinoma, Hepatocellular. | en_US |
dc.subject.lcsh | Cancer--Genetic aspects. | en_US |
dc.subject.lcsh | DNA-Protein interaction. | en_US |
dc.subject.lcsh | Protein interaction. | en_US |
dc.subject.lcsh | Cancer cells. | en_US |
dc.subject.lcsh | p53 antioncogene. | en_US |
dc.subject.lcsh | Liver cancer. | en_US |
dc.subject.lcsh | Endoplasmic reticulum. | en_US |
dc.subject.lcsh | Carcinogenesis. | en_US |
dc.title | Characterization of FAM134B in the context of hepatocellular carcinoma and endoplasmic reticulum protein stress | en_US |
dc.type | Thesis | en_US |
dc.department | Department of Molecular Biology and Genetics | en_US |
dc.publisher | Bilkent University | en_US |
dc.description.degree | M.S. | en_US |