{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/87253"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/87253","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"DNA Repair, Redox Regulation and Modulation of Estrogen Receptor Alpha Mediated Transcription","abstract":"Interaction of estrogen receptor alpha (ERalpha) with 17beta-estradiol (E2) facilitates binding of the receptor to estrogen response elements (EREs) in target genes, which in turn leads to recruitment of coregulatory proteins. To better understand how estrogen-responsive genes are regulated, our laboratory identified a number of proteins that associate with the DNA-bound ERalpha. Our studies demonstrate that the nonmetastatic protein 23 homolog 1 (NM23-H1) interacts with ERalpha, increases ERalpha-ERE complex formation, influences ERalpha-mediated transcription and associates with the promoter region of the endogenous estrogen-responsive progesterone receptor (PR) gene. Furthermore, we show that a second protein, Apurinic/apyrimidinic endonuclease 1 or redox factor-1 (Ape1/Ref-1), interacts with ERalpha, promotes the ERalpha-ERE interaction, influences ERalpha-mediated transactivation, and selectively associates with endogenous, estrogen-responsive genes in MCF-7 cells. Our findings suggest that NM23-H1 and Ape1/Ref-1 are instrumental in modulating expression of estrogen-responsive genes. Interestingly, we demonstrate that Ape1/Ref-1 and NM23-H1, as well as the oxidative stress proteins Cu/Zn superoxide dismutase (SOD1), thioredoxin (Trx) and protein disulfide isomerase (PDI) are overexpressed in human breast cancer tissues. These studies provide a novel link between DNA repair, redox regulation and modulation of ERalpha-mediated transcription.","abstract_html":"Interaction of estrogen receptor alpha (ERalpha) with 17beta-estradiol (E2) facilitates binding of the receptor to estrogen response elements (EREs) in target genes, which in turn leads to recruitment of coregulatory proteins. To better understand how estrogen-responsive genes are regulated, our laboratory identified a number of proteins that associate with the DNA-bound ERalpha. Our studies demonstrate that the nonmetastatic protein 23 homolog 1 (NM23-H1) interacts with ERalpha, increases ERalpha-ERE complex formation, influences ERalpha-mediated transcription and associates with the promoter region of the endogenous estrogen-responsive progesterone receptor (PR) gene. Furthermore, we show that a second protein, Apurinic/apyrimidinic endonuclease 1 or redox factor-1 (Ape1/Ref-1), interacts with ERalpha, promotes the ERalpha-ERE interaction, influences ERalpha-mediated transactivation, and selectively associates with endogenous, estrogen-responsive genes in MCF-7 cells. Our findings suggest that NM23-H1 and Ape1/Ref-1 are instrumental in modulating expression of estrogen-responsive genes. Interestingly, we demonstrate that Ape1/Ref-1 and NM23-H1, as well as the oxidative stress proteins Cu/Zn superoxide dismutase (SOD1), thioredoxin (Trx) and protein disulfide isomerase (PDI) are overexpressed in human breast cancer tissues. These studies provide a novel link between DNA repair, redox regulation and modulation of ERalpha-mediated transcription.","abstract_has_math":false,"creators":["Curtis-Ducey, Carol Dianne"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Molecular and Integrative Physiology","degree_department":null,"school":null,"contributors":["Nardulli, Ann M."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-09-28T15:50:14Z","date_published":"2015-09-28T15:50:14Z","updated_at":"2026-07-22T22:26:28Z","subjects":["Biology, Physiology"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(MiAaPQ)AAI3391919"],"render_values":[{"text":"(MiAaPQ)AAI3391919","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/87253","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Nardulli, Ann M."]},{"key":"dc:creator","label":"Author","values":["Curtis-Ducey, Carol Dianne"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2015-09-28T15:50:14Z","10000-01-01","2009"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Molecular and Integrative Physiology"]},{"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, Physiology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/87253","(MiAaPQ)AAI3391919"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Interaction of estrogen receptor alpha (ERalpha) with 17beta-estradiol (E2) facilitates binding of the receptor to estrogen response elements (EREs) in target genes, which in turn leads to recruitment of coregulatory proteins. To better understand how estrogen-responsive genes are regulated, our laboratory identified a number of proteins that associate with the DNA-bound ERalpha. Our studies demonstrate that the nonmetastatic protein 23 homolog 1 (NM23-H1) interacts with ERalpha, increases ERalpha-ERE complex formation, influences ERalpha-mediated transcription and associates with the promoter region of the endogenous estrogen-responsive progesterone receptor (PR) gene. Furthermore, we show that a second protein, Apurinic/apyrimidinic endonuclease 1 or redox factor-1 (Ape1/Ref-1), interacts with ERalpha, promotes the ERalpha-ERE interaction, influences ERalpha-mediated transactivation, and selectively associates with endogenous, estrogen-responsive genes in MCF-7 cells. Our findings suggest that NM23-H1 and Ape1/Ref-1 are instrumental in modulating expression of estrogen-responsive genes. Interestingly, we demonstrate that Ape1/Ref-1 and NM23-H1, as well as the oxidative stress proteins Cu/Zn superoxide dismutase (SOD1), thioredoxin (Trx) and protein disulfide isomerase (PDI) are overexpressed in human breast cancer tissues. These studies provide a novel link between DNA repair, redox regulation and modulation of ERalpha-mediated transcription.","Made available in DSpace on 2015-09-28T15:50:14Z (GMT). No. of bitstreams: 2 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 3391919.pdf: 1204690 bytes, checksum: e8a801697c3f92719540610e8a73188a (MD5) Previous issue date: 2009","Embargo set by: Seth Robbins for item 88534 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","75 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2009."]},{"key":"dc:title","label":"Title","values":["DNA Repair, Redox Regulation and Modulation of Estrogen Receptor Alpha Mediated Transcription"]}]}],"canonical_facts":{"dc:contributor":["Nardulli, Ann M."],"dc:creator":["Curtis-Ducey, Carol Dianne"],"dc:date":["2015-09-28T15:50:14Z","10000-01-01","2009"],"dc:description":["Interaction of estrogen receptor alpha (ERalpha) with 17beta-estradiol (E2) facilitates binding of the receptor to estrogen response elements (EREs) in target genes, which in turn leads to recruitment of coregulatory proteins. To better understand how estrogen-responsive genes are regulated, our laboratory identified a number of proteins that associate with the DNA-bound ERalpha. Our studies demonstrate that the nonmetastatic protein 23 homolog 1 (NM23-H1) interacts with ERalpha, increases ERalpha-ERE complex formation, influences ERalpha-mediated transcription and associates with the promoter region of the endogenous estrogen-responsive progesterone receptor (PR) gene. Furthermore, we show that a second protein, Apurinic/apyrimidinic endonuclease 1 or redox factor-1 (Ape1/Ref-1), interacts with ERalpha, promotes the ERalpha-ERE interaction, influences ERalpha-mediated transactivation, and selectively associates with endogenous, estrogen-responsive genes in MCF-7 cells. Our findings suggest that NM23-H1 and Ape1/Ref-1 are instrumental in modulating expression of estrogen-responsive genes. Interestingly, we demonstrate that Ape1/Ref-1 and NM23-H1, as well as the oxidative stress proteins Cu/Zn superoxide dismutase (SOD1), thioredoxin (Trx) and protein disulfide isomerase (PDI) are overexpressed in human breast cancer tissues. These studies provide a novel link between DNA repair, redox regulation and modulation of ERalpha-mediated transcription.","Made available in DSpace on 2015-09-28T15:50:14Z (GMT). No. of bitstreams: 2 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 3391919.pdf: 1204690 bytes, checksum: e8a801697c3f92719540610e8a73188a (MD5) Previous issue date: 2009","Embargo set by: Seth Robbins for item 88534 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","75 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2009."],"dc:identifier":["http://hdl.handle.net/2142/87253","(MiAaPQ)AAI3391919"],"dc:language":["eng"],"dc:subject":["Biology, Physiology"],"dc:title":["DNA Repair, Redox Regulation and Modulation of Estrogen Receptor Alpha Mediated Transcription"],"dc:type":["text"],"thesis:degree_discipline":["Molecular and Integrative Physiology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:26:28Z"}