Characterization of chemosensitivity profiles of breast cancer cell lınes, with and without stem cell like features = Kök-hücre özelliği olan ve olmayan meme kanseri hücre hatlarının ilaç hassasiyet profillerinin tanımlanması

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buir.advisorGüre, Ali Osmay
dc.contributor.authorAkbar, Muhammad Waqas
dc.date.accessioned2016-01-08T20:18:18Z
dc.date.available2016-01-08T20:18:18Z
dc.date.issued2014
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.descriptionAnkara : The Department of Molecular Biology and Genetics and the Graduate School of Engineering and Science of Bilkent University, 2014.en_US
dc.descriptionThesis (Master's) -- Bilkent University, 2014.en_US
dc.descriptionIncludes bibliographical references leaves 78-82.en_US
dc.description.abstractBreast cancer is the second most common cause of death worldwide from cancer due to complications with its diagnosis and resistance to therapy. Recent studies have shown that breast tumors when compared with other solid tumors also contain a subpopulation termed as cancer stem cells (CSCs). CSCs are hard to kill due to their therapy resistant capacities. These unharmed cells then result into relapse of tumor after treatment. Some established breast cancer cell lines also behave in similar fashion to CSCs in overall manner thus termed as CSC like cell lines. This study primarily focuses on characterizing CSC like cell lines from non CSC like cell lines based upon their gene expression and prediction of drugs which can target these groups separately. In this study two databases, Cancer Cell Line Encyclopedia (CCLE) and Cancer Genome Project (CGP), were used which contain gene expression data and drugs cytotoxicity data for most of the established cancer cell lines. Breast cancer cell lines gene expression data was used to predict two gene lists which can separate breast cancer cell lines into CSC like and non CSC like cell lines by in silico analysis. These gene lists were named as Patentable and Non Patentable. Additionally four drugs were predicted which can target CSC like group (Midostaurin and Elesclomol) and non CSC like group (Panobinostat and Lapatinib) separately. Later these findings were validated in vitro. Non Patentable gene list could not be validated due to low concordance with microarray data. On the other hand, Patentable gene list was validated and was found concordant with microarray data. Out of four selected drugs, Panobinostat and Lapatinib showed increased toxicity to non CSC like cell lines while only Midostaurin showed toxicity to CSC like cell lines. To investigate further that cell lines were grown in 3D cell culture conditions, to increase their stem cell like properties (stemness). But only one cell line MDA-MB-157 which was found as CSC like, showed expected behavior. Additionally this cell line increased resistance to Lapatinib and Panobinostat and became more sensitive to Midostaurin. Correlation analysis showed some genes as potential biomarkers for selected drugs. In conclusion, in this study various genes are proposed to differentiate CSC like cell lines from non CSC like cell lines. And Midostaurin can be potential drug to treat CSC like cells while Lapatinib and Panobinostat showed increased activity against non CSC like cell lines.en_US
dc.description.degreeM.S.en_US
dc.description.statementofresponsibilityAkbar, Muhammad Waqasen_US
dc.embargo.release2016-09-01
dc.format.extentxvi, 107 leaves, charts, plates, illustrationsen_US
dc.identifier.itemidB148311
dc.identifier.urihttp://hdl.handle.net/11693/18326
dc.language.isoEnglishen_US
dc.publisherBilkent Universityen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectBreast canceren_US
dc.subjectCancer stem cellsen_US
dc.subjectMidostaurinen_US
dc.subjectElesclomolen_US
dc.subjectLapatiniben_US
dc.subjectPanobinostaten_US
dc.subjectMammosphereen_US
dc.subjectCCLEen_US
dc.subjectCGPen_US
dc.subjectqPCRen_US
dc.subject3D cell cultureen_US
dc.subject.lccQZ202 .A43 2014en_US
dc.subject.lcshCancer cells.en_US
dc.subject.lcshStem cells.en_US
dc.subject.lcshCancer--Chemotherapy.en_US
dc.subject.lcshAntineoplastic agents.en_US
dc.subject.lcshCell culture--Technique.en_US
dc.titleCharacterization of chemosensitivity profiles of breast cancer cell lınes, with and without stem cell like features = Kök-hücre özelliği olan ve olmayan meme kanseri hücre hatlarının ilaç hassasiyet profillerinin tanımlanmasıen_US
dc.typeThesisen_US
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