{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/86736"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/86736","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Effects of Mesenchymal Transition on Sensitivity of Breast Cancer Cells to LT-IIc","abstract":"M.S.","abstract_html":"M.S.","abstract_has_math":false,"creators":["Madhurabaratula, Nandita Ramprasad"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Masso-Welch, Patricia","Biotechnical and Clinical Laboratory Sciences"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-02-21T21:44:34Z","date_published":"2025-02-21T21:44:34Z","updated_at":"2026-07-27T19:05:34Z","subjects":["cellular biology","biology","oncology"],"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/10477/86736","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Masso-Welch, Patricia","Biotechnical and Clinical Laboratory Sciences"]},{"key":"dc:creator","label":"Author","values":["Madhurabaratula, Nandita Ramprasad"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-02-21T21:44:34Z","2020"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["cellular biology","biology","oncology"]}]},{"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/10477/86736"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["M.S.","The epithelial to mesenchymal transition (EMT) is a cellular program wherein epithelial cells acquire motility and invasiveness, similar to the activity of mesenchymal cells. Triple negative breast cancer (TNBC) is the most lethal form of breast cancer, with a high rate of metastasis, recurrence and mortality. LT-IIc is a bacterial enterotoxin that induces cytotoxicity in mesenchymal transformed (TM12T) but not epithelioid (TM12) clonally derived mouse breast cancer cell lines. It induces toxicity in and human breast cancer cell lines with a mesenchymal TNBC phenotype as well. The purpose of this thesis was to test the hypothesis that the mesenchymal phenotype is sufficient for inducing sensitivity to LT-IIc. To test this hypothesis, we used in vitro models of EMT induction. In the normally LT-IIc resistant epithelial MCF10A and MCF-7 cell lines, TGF-beta treatment alone was not sufficient to induce lasting EMT. A commercial EMT- media supplement targeting the TGF beta plus cadherin-dependent signaling pathway successfully induced EMT. This transition was confirmed by changes in cellular morphology and differential expression of epithelioid versus mesenchymal markers. After the transition, cells were observed to lose their epithelial morphology, and to adopt a mesenchymal-like appearance. The epithelial marker (E-cadherin) was reduced after EMT treatment and the presence of mesenchymal markers (transcription factors SNAI, ZEB1) was observed. The transitioned cells were tested for LT-IIc susceptibility by induction of cellular vacuolization (indicating induction of autophagy and blocking of lysosomal progression), and MTT assay. The LT-IIc holotoxin, (catalytic A subunit and ganglioside binding B5 pentamer) was compared to the B5 pentamer alone. Induction of EMT was sufficient to induce LT-IIc vacuolization and cytotoxicity, and cells were more sensitive to killing by the B5 pentamer than the holotoxin. These results suggest that LT-IIc-targeted ganglioside signaling pathways may be novel targets for chemotherapy of mesenchymal TNBC.","**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":["Effects of Mesenchymal Transition on Sensitivity of Breast Cancer Cells to LT-IIc"]}]}],"canonical_facts":{"dc:contributor":["Masso-Welch, Patricia","Biotechnical and Clinical Laboratory Sciences"],"dc:creator":["Madhurabaratula, Nandita Ramprasad"],"dc:date":["2025-02-21T21:44:34Z","2020"],"dc:description":["M.S.","The epithelial to mesenchymal transition (EMT) is a cellular program wherein epithelial cells acquire motility and invasiveness, similar to the activity of mesenchymal cells. Triple negative breast cancer (TNBC) is the most lethal form of breast cancer, with a high rate of metastasis, recurrence and mortality. LT-IIc is a bacterial enterotoxin that induces cytotoxicity in mesenchymal transformed (TM12T) but not epithelioid (TM12) clonally derived mouse breast cancer cell lines. It induces toxicity in and human breast cancer cell lines with a mesenchymal TNBC phenotype as well. The purpose of this thesis was to test the hypothesis that the mesenchymal phenotype is sufficient for inducing sensitivity to LT-IIc. To test this hypothesis, we used in vitro models of EMT induction. In the normally LT-IIc resistant epithelial MCF10A and MCF-7 cell lines, TGF-beta treatment alone was not sufficient to induce lasting EMT. A commercial EMT- media supplement targeting the TGF beta plus cadherin-dependent signaling pathway successfully induced EMT. This transition was confirmed by changes in cellular morphology and differential expression of epithelioid versus mesenchymal markers. After the transition, cells were observed to lose their epithelial morphology, and to adopt a mesenchymal-like appearance. The epithelial marker (E-cadherin) was reduced after EMT treatment and the presence of mesenchymal markers (transcription factors SNAI, ZEB1) was observed. The transitioned cells were tested for LT-IIc susceptibility by induction of cellular vacuolization (indicating induction of autophagy and blocking of lysosomal progression), and MTT assay. The LT-IIc holotoxin, (catalytic A subunit and ganglioside binding B5 pentamer) was compared to the B5 pentamer alone. Induction of EMT was sufficient to induce LT-IIc vacuolization and cytotoxicity, and cells were more sensitive to killing by the B5 pentamer than the holotoxin. These results suggest that LT-IIc-targeted ganglioside signaling pathways may be novel targets for chemotherapy of mesenchymal TNBC.","**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/10477/86736"],"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":["cellular biology","biology","oncology"],"dc:title":["Effects of Mesenchymal Transition on Sensitivity of Breast Cancer Cells to LT-IIc"],"dc:type":["Text","Thesis"]},"updated_at":"2026-07-27T19:05:34Z"}