{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/72488"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/72488","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"A Novel Link Between Oxidative Stress Proteins and Estrogen Receptor Alpha-Mediated Gene Expression","abstract":"The classical genomic pathway for 17beta-estradiol (E 2) action involves binding to estrogen receptor alpha (ERalpha) in target cells, interaction with estrogen response element (ERE)-containing DNA, recruitment of coregulatory proteins, and modification of estrogen responsive genes. Because DNA-induced conformational changes in ERalpha structure alter complex formation, we were interested in identifying proteins associated with the ERE-bound receptor. Using a novel electrophoretic fractionation method, we identified a number of proteins involved in oxidative stress response including Cu/Zn superoxide dismutase (SOD1), thioredoxin (Trx) and thioredoxin reductase (TrxR). We found that SOD1 interacts with ERalpha, enhances ERalpha-ERE complex formation, influences estrogen responsiveness and associates with estrogen responsive regions of the pS2 and progesterone receptor genes. Furthermore, when MCF-7 breast cancer cells are exposed to E2 and superoxide SOD1 levels increase and oxidative stress-induced protein damage is greatly reduced. We also demonstrate that endogenously-expressed ERalpha, Trx, and TrxR interact, differentially influence endogenous estrogen-responsive gene expression, and alter hydrogen peroxide levels in MCF-7 cells. Additional characterization using brain slice cultures suggests a protective role for E2 and SOD1 in the cerebral cortex. These combined studies highlight a novel link between oxidative stress proteins and ERalpha-mediated gene expression in target tissues.","abstract_html":"The classical genomic pathway for 17beta-estradiol (E 2) action involves binding to estrogen receptor alpha (ERalpha) in target cells, interaction with estrogen response element (ERE)-containing DNA, recruitment of coregulatory proteins, and modification of estrogen responsive genes. Because DNA-induced conformational changes in ERalpha structure alter complex formation, we were interested in identifying proteins associated with the ERE-bound receptor. Using a novel electrophoretic fractionation method, we identified a number of proteins involved in oxidative stress response including Cu/Zn superoxide dismutase (SOD1), thioredoxin (Trx) and thioredoxin reductase (TrxR). We found that SOD1 interacts with ERalpha, enhances ERalpha-ERE complex formation, influences estrogen responsiveness and associates with estrogen responsive regions of the pS2 and progesterone receptor genes. Furthermore, when MCF-7 breast cancer cells are exposed to E2 and superoxide SOD1 levels increase and oxidative stress-induced protein damage is greatly reduced. We also demonstrate that endogenously-expressed ERalpha, Trx, and TrxR interact, differentially influence endogenous estrogen-responsive gene expression, and alter hydrogen peroxide levels in MCF-7 cells. Additional characterization using brain slice cultures suggests a protective role for E2 and SOD1 in the cerebral cortex. These combined studies highlight a novel link between oxidative stress proteins and ERalpha-mediated gene expression in target tissues.","abstract_has_math":false,"creators":["Rao, Abhilasha"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Cell and Developmental Biology","degree_department":null,"school":null,"contributors":["Katzenellenbogen, Benita S.","Nardulli, Ann M."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2014,"date_issued":"2014-12-17T22:58:20Z","date_published":"2014-12-17T22:58:20Z","updated_at":"2026-07-22T22:26:06Z","subjects":["Biology, Molecular","Biology, Physiology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(UMI)AAI3392443"],"render_values":[{"text":"(UMI)AAI3392443","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/72488","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Katzenellenbogen, Benita S.","Nardulli, Ann M."]},{"key":"dc:creator","label":"Author","values":["Rao, Abhilasha"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2014-12-17T22:58:20Z","10000-01-01","2009"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Cell and Developmental Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology, Molecular","Biology, Physiology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/72488","(UMI)AAI3392443"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The classical genomic pathway for 17beta-estradiol (E 2) action involves binding to estrogen receptor alpha (ERalpha) in target cells, interaction with estrogen response element (ERE)-containing DNA, recruitment of coregulatory proteins, and modification of estrogen responsive genes. Because DNA-induced conformational changes in ERalpha structure alter complex formation, we were interested in identifying proteins associated with the ERE-bound receptor. Using a novel electrophoretic fractionation method, we identified a number of proteins involved in oxidative stress response including Cu/Zn superoxide dismutase (SOD1), thioredoxin (Trx) and thioredoxin reductase (TrxR). We found that SOD1 interacts with ERalpha, enhances ERalpha-ERE complex formation, influences estrogen responsiveness and associates with estrogen responsive regions of the pS2 and progesterone receptor genes. Furthermore, when MCF-7 breast cancer cells are exposed to E2 and superoxide SOD1 levels increase and oxidative stress-induced protein damage is greatly reduced. We also demonstrate that endogenously-expressed ERalpha, Trx, and TrxR interact, differentially influence endogenous estrogen-responsive gene expression, and alter hydrogen peroxide levels in MCF-7 cells. Additional characterization using brain slice cultures suggests a protective role for E2 and SOD1 in the cerebral cortex. These combined studies highlight a novel link between oxidative stress proteins and ERalpha-mediated gene expression in target tissues.","Made available in DSpace on 2014-12-17T22:58:20Z (GMT). No. of bitstreams: 1 3392443.pdf: 1153354 bytes, checksum: 173961dc240994ea03cf395110b6e1f1 (MD5) Previous issue date: 2009","Embargo set by: Seth Robbins for item 72656 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","68 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2009."]},{"key":"dc:title","label":"Title","values":["A Novel Link Between Oxidative Stress Proteins and Estrogen Receptor Alpha-Mediated Gene Expression"]}]}],"canonical_facts":{"dc:contributor":["Katzenellenbogen, Benita S.","Nardulli, Ann M."],"dc:creator":["Rao, Abhilasha"],"dc:date":["2014-12-17T22:58:20Z","10000-01-01","2009"],"dc:description":["The classical genomic pathway for 17beta-estradiol (E 2) action involves binding to estrogen receptor alpha (ERalpha) in target cells, interaction with estrogen response element (ERE)-containing DNA, recruitment of coregulatory proteins, and modification of estrogen responsive genes. Because DNA-induced conformational changes in ERalpha structure alter complex formation, we were interested in identifying proteins associated with the ERE-bound receptor. Using a novel electrophoretic fractionation method, we identified a number of proteins involved in oxidative stress response including Cu/Zn superoxide dismutase (SOD1), thioredoxin (Trx) and thioredoxin reductase (TrxR). We found that SOD1 interacts with ERalpha, enhances ERalpha-ERE complex formation, influences estrogen responsiveness and associates with estrogen responsive regions of the pS2 and progesterone receptor genes. Furthermore, when MCF-7 breast cancer cells are exposed to E2 and superoxide SOD1 levels increase and oxidative stress-induced protein damage is greatly reduced. We also demonstrate that endogenously-expressed ERalpha, Trx, and TrxR interact, differentially influence endogenous estrogen-responsive gene expression, and alter hydrogen peroxide levels in MCF-7 cells. Additional characterization using brain slice cultures suggests a protective role for E2 and SOD1 in the cerebral cortex. These combined studies highlight a novel link between oxidative stress proteins and ERalpha-mediated gene expression in target tissues.","Made available in DSpace on 2014-12-17T22:58:20Z (GMT). No. of bitstreams: 1 3392443.pdf: 1153354 bytes, checksum: 173961dc240994ea03cf395110b6e1f1 (MD5) Previous issue date: 2009","Embargo set by: Seth Robbins for item 72656 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs","U of I Only","68 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2009."],"dc:identifier":["http://hdl.handle.net/2142/72488","(UMI)AAI3392443"],"dc:subject":["Biology, Molecular","Biology, Physiology"],"dc:title":["A Novel Link Between Oxidative Stress Proteins and Estrogen Receptor Alpha-Mediated Gene Expression"],"dc:type":["text"],"thesis:degree_discipline":["Cell and Developmental Biology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:26:06Z"}