Show simple item record

dc.contributor.advisorGüre, Ali Osmayen_US
dc.contributor.authorKüçükkaraduman, Barışen_US
dc.date.accessioned2016-08-29T08:32:37Z
dc.date.available2016-08-29T08:32:37Z
dc.date.copyright2016-08
dc.date.issued2016-08
dc.date.submitted2016-08-25
dc.identifier.urihttp://hdl.handle.net/11693/32177
dc.descriptionCataloged from PDF version of article.en_US
dc.descriptionThesis (M.S.): Bilkent University, Department of Molecular Biology and Genetics, İhsan Doğramacı Bilkent University, 2016.en_US
dc.descriptionIncludes bibliographical references (leaves 63-69).en_US
dc.description.abstractEpigenetic aberrations are frequently observed in cancer. Tumor-suppressor genes are often repressed with anomalous hypermethylation in cancer, while DNA hypomethylation has been identified in repetitive sequences and promoter regions of cancer testis (CT) genes resulting in genomic instability. Although it has been shown that CT genes are often regulated by dissociation of repressive proteins from promoter-proximal regions and epigenetic mechanisms, including DNA methylation, histone methylation and acetylation, the process leading to epigenetic changes and de-repression of CT genes remains largely unknown. This study aimed to reveal molecular mechanisms which may have role in coordinating CT gene expression. For this purpose, we designed two groups of experiments. The first was based on extending our previous observations related to two genes (ALAS2, CDR1) which showed inverse expression patterns, compared to CT genes in cancer cell lines. The ex vivo analysis of expression patterns of these genes, however, did not support an inverse relation between their expression and that of CT genes. The second approach was based on categorizing cancer cells into CT-high, CT-intermediate and CT-low groups to define differentially expressed non-CT genes that could help explain mechanisms underlying epigenetic changes and subsequent activation of CT genes. Surprisingly, we could not identify any transcripts that differentially expressed between these subgroups. We therefore, hypothesized that non-overlapping and distinct mechanisms could be involved in the upregulation of CT genes in different tumors. As our earlier work suggested a relationship between epithelial to mesenchymal transition (EMT) and CT expression we asked if an EMT based classification could help elucidate these mechanisms. Indeed, differential genes and differentially activated signaling pathways were discovered when cancer cells were first grouped by their EMT status. This helped us identify candidate proteins (BMI1, PCGF2, RB1 and RBL1) and pathways including MAPK/ERK and PTEN/PI3K pathways which can coordinate CT gene expression in cancer. Thirdly, we investigated clinical relevance of high CT gene expression in triple negative breast cancer by attempting to correlate this with drug sensitivity. Drug sensitivity against panobinostat showed correlation with CT gene expression. In summary, this study suggests new approaches to elucidate mechanisms which coordinate epigenetic aberrations in cancer and how these can be utilized for cancer therapy.en_US
dc.description.statementofresponsibilityby Barış Küçükkaraduman.en_US
dc.format.extentxvi, 85 leaves :|bcharts, graphics (some color).en_US
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCancer testis genesen_US
dc.subjectDNA methylationen_US
dc.subjectEpithelial and mesenchymal phenotypeen_US
dc.subjectPanobinostaten_US
dc.titleIdentification of a novel experimental model to reveal mechanisms leading to epigenetic changes and subsequent activation of cancer testis genes in canceren_US
dc.title.alternativeKanserde epigenetik değişimlere ve sonrasında kanser testis genlerinin aktivasyonuna sebep olan mekanizmaların ortaya çıkarılması için yeni deneysel modellerin tanımlanmasıen_US
dc.typeThesisen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.publisherBilkent Universityen_US
dc.description.degreeM.S.en_US
dc.identifier.itemidB153996


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record