{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/79948"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/79948","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Characterizing the Role of Histone Chaperone Fact in Breast Cancer Development and Progression","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Prendergast, Laura; 0000-0003-0467-657X"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Gurova, Katerina","Roswell Park"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-07-30T15:11:20Z","date_published":"2019-07-30T15:11:20Z","updated_at":"2026-07-27T19:05:21Z","subjects":["molecular biology","cellular biology"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/79948","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Gurova, Katerina","Roswell Park"]},{"key":"dc:creator","label":"Author","values":["Prendergast, Laura; 0000-0003-0467-657X"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-07-30T15:11:20Z","2019","2019-05-15 13:09:25"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["molecular biology","cellular biology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/79948"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","FACT (Facilitates Chromatin Transcription) is histone chaperone which was shown to play a role in DNA replication, repair, and transcription. FACT function was extensively studied in cell-free systems and single cell models, such as yeast cells and metazoan cell lines, where it was essential for viability of these cells. However, studies done in higher eukaryotes on the organismal level resulted in two major observations which challenge that this notion is true for all cells: (i) far from all cells in animals and plants express FACT in basal conditions, and (ii) depletion of FACT does not always have a significant phenotype or result in loss of viability. These findings have challenged the assumption that FACT is essential for all DNA replication or transcription. It was also shown that FACT is highly expressed in multiple tumors of different types. In some cancers, e.g. breast adenocarcinoma, higher protein levels of FACT correlate with known markers of poor prognosis, presence of metastatic disease, and poor overall survival. Moreover, knockdown or inhibition of FACT is toxic to tumor cells, but much less toxic for non-tumor cells, suggesting that during tumorigenesis cells acquire FACT dependence. Though, the mechanism by which FACT supports tumor cell viability has remained elusive. The main objective of this dissertation was to understand how expression of the histone chaperone FACT contributes to breast cancer development and progression. Breast cancer was selected as a model for this study due to the prevalence of early stage disease with few biomarkers to predict aggressive potential, the lack of targeted therapies for some aggressive subtypes, and a previous study showing that treatment of MMTV-neu mice, a model of aggressive BrCa, with small molecule inhibitors of FACT reduced the incidence of mammary tumors, delayed tumor progression, and prolonged survival of mice. Three specific aims were designed to approach the research objective: (1) characterize the prognostic value of FACT in breast cancer diagnosis; (2) determine the consequences of FACT loss in breast tumor cells; (3) understand why FACT is essential for viability and growth of breast cancer cells.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Characterizing the Role of Histone Chaperone Fact in Breast Cancer Development and Progression"]}]}],"canonical_facts":{"dc:contributor":["Gurova, Katerina","Roswell Park"],"dc:creator":["Prendergast, Laura; 0000-0003-0467-657X"],"dc:date":["2019-07-30T15:11:20Z","2019","2019-05-15 13:09:25"],"dc:description":["Ph.D.","FACT (Facilitates Chromatin Transcription) is histone chaperone which was shown to play a role in DNA replication, repair, and transcription. FACT function was extensively studied in cell-free systems and single cell models, such as yeast cells and metazoan cell lines, where it was essential for viability of these cells. However, studies done in higher eukaryotes on the organismal level resulted in two major observations which challenge that this notion is true for all cells: (i) far from all cells in animals and plants express FACT in basal conditions, and (ii) depletion of FACT does not always have a significant phenotype or result in loss of viability. These findings have challenged the assumption that FACT is essential for all DNA replication or transcription. It was also shown that FACT is highly expressed in multiple tumors of different types. In some cancers, e.g. breast adenocarcinoma, higher protein levels of FACT correlate with known markers of poor prognosis, presence of metastatic disease, and poor overall survival. Moreover, knockdown or inhibition of FACT is toxic to tumor cells, but much less toxic for non-tumor cells, suggesting that during tumorigenesis cells acquire FACT dependence. Though, the mechanism by which FACT supports tumor cell viability has remained elusive. The main objective of this dissertation was to understand how expression of the histone chaperone FACT contributes to breast cancer development and progression. Breast cancer was selected as a model for this study due to the prevalence of early stage disease with few biomarkers to predict aggressive potential, the lack of targeted therapies for some aggressive subtypes, and a previous study showing that treatment of MMTV-neu mice, a model of aggressive BrCa, with small molecule inhibitors of FACT reduced the incidence of mammary tumors, delayed tumor progression, and prolonged survival of mice. Three specific aims were designed to approach the research objective: (1) characterize the prognostic value of FACT in breast cancer diagnosis; (2) determine the consequences of FACT loss in breast tumor cells; (3) understand why FACT is essential for viability and growth of breast cancer cells.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/79948"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["molecular biology","cellular biology"],"dc:title":["Characterizing the Role of Histone Chaperone Fact in Breast Cancer Development and Progression"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:21Z"}