Analysis of the ATAD2 gene effect on the genes involved in epithelial mesenchymal transition in estrogen positive and negative breast cancers
buir.advisor | Yuluğ, Işık | |
dc.contributor.author | Özerk, Zeynep Ilgım | |
dc.date.accessioned | 2021-02-15T07:53:40Z | |
dc.date.available | 2021-02-15T07:53:40Z | |
dc.date.copyright | 2021-02 | |
dc.date.issued | 2021-02 | |
dc.date.submitted | 2021-02-10 | |
dc.description | Cataloged from PDF version of article. | en_US |
dc.description | Thesis (M.S.): Bilkent University, Department of Molecular Biology and Genetics, İhsan Doğramacı Bilkent University, 2021. | en_US |
dc.description | Includes bibliographical references (leaves 58-62). | en_US |
dc.description.abstract | ATAD2 is overexpressed in many distinct cancer types including breast cancer. Its elevated expression is an indicator of poor prognosis. High ATAD2 expression correlates with short overall survival, disease-free survival as well as shorter recurrence-free survival. Moreover, ATAD2 is associated with migration and invasion in some cancer types such as hepatocellular carcinoma and cervical cancer. In breast cancer, ATAD2 expression is higher in invasive tumors. ATAD2 is coactivator of steroid hormone receptor ERα. It directly interacts with ERα and enhances its target genes expressions. ERα is also a regulator of EMT in breast carcinomas. Based on our current knowledge it is proposed that ATAD2 may have a role in EMT and migration capacity of breast cancer cells and this role may be ER dependent as both ATAD2 and EMT are associated with ERα. Bioinformatics analysis revealed that siATAD2 silencing decreased mesenchymal gene expressions significantly in MCF7 and T47D cells. To investigate the possible mesenchymal inducing role of ATAD2, ATAD2 was silenced with shRNA transfection in ER+ MCF7 and T47D cells and ER- mda-mb-231 and sk-br-3 cells. ATAD2 silencing decreased mesenchymal markers expression at both the mRNA and protein level in ER- cells. In ER+ cells, no change in EMT marker proteins and mRNAs were observed with ATAD2 silencing. ER was silenced in ER+ cells and ER silencing introduced a mesenchymal phenotype to them. In this case, ATAD2 silencing reduced this mesenchymal phenotype introduced with ER loss. The EMT effect of the ATAD2 silencing on migration capacity of breast cancer cells was assessed with a scratch assay. Consistent with changes in the epithelial and mesenchymal markers, ATAD2 silencing reduced the migration capacity of mda-mb-231 cells. On the other hand, sk-br-3 migration did not change significantly. In ER+ cells ATAD2 silencing alone had no influence on migratory capacity. ER silencing increased their migration significantly while ATAD2 downregulation in ER-silenced cells suppressed this migration. Over all, this study suggests a possible involvement of ATAD2 in EMT and migration regulation in ER- cells. Targeting ATAD2 in ER- mesenchymal breast cancer cells could be a strategy to reduce their migration capacity. | en_US |
dc.description.provenance | Submitted by Betül Özen (ozen@bilkent.edu.tr) on 2021-02-15T07:53:40Z No. of bitstreams: 1 10380198.pdf: 3353708 bytes, checksum: e8750f86143793e88fa3b49a1b42ee15 (MD5) | en |
dc.description.provenance | Made available in DSpace on 2021-02-15T07:53:40Z (GMT). No. of bitstreams: 1 10380198.pdf: 3353708 bytes, checksum: e8750f86143793e88fa3b49a1b42ee15 (MD5) Previous issue date: 2021-02 | en |
dc.description.statementofresponsibility | by Zeynep Ilgım Özerk | en_US |
dc.format.extent | xi, 72 leaves : color illustrations, charts, graphics ; 30 cm. | en_US |
dc.identifier.itemid | B150681 | |
dc.identifier.uri | http://hdl.handle.net/11693/55130 | |
dc.language.iso | English | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | ATAD2 | en_US |
dc.subject | ERα | en_US |
dc.subject | Breast cancer | en_US |
dc.subject | EMT | en_US |
dc.subject | Migration | en_US |
dc.title | Analysis of the ATAD2 gene effect on the genes involved in epithelial mesenchymal transition in estrogen positive and negative breast cancers | en_US |
dc.title.alternative | Östrojen pozitif ve negatif meme kanserinde ATAD2 geninin epitel mezenkimal dönüşüm genleri üzerine etkisinin analizi | en_US |
dc.type | Thesis | en_US |
thesis.degree.discipline | Molecular Biology and Genetics | |
thesis.degree.grantor | Bilkent University | |
thesis.degree.level | Master's | |
thesis.degree.name | MS (Master of Science) |