{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/84854"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/84854","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Estrogen Inducible Proteinase Inhibitor 9 Protects Target Cells From Immune Surveillance and Apoptosis","abstract":"To test the effect of estrogen receptor (ER) ligands that induce PI-9 on TRAIL-mediated cytotoxicity, we used MCF-7, human breast cancer cells. In MCF-7 cells, induction of PI-9 by 17beta-estradiol (E2) inhibited TRAIL-mediated cytotoxicity. This is the first demonstration that regulation of PI-9 expression from its endogenous promoter results in production of sufficient PI-9 to inhibit cytotoxocity by members of the TNF superfamily. To test the effect of the selective estrogen receptor modulator (SERM), 4-hydroxytamoxifen (OHT) (the active metabolite of tamoxifen), we used a tet-inducible MCF-7 cell model system, termed MCF7ERalphaHA cells. In MCF7ERalphaHA cells, OHT is a full agonist and induces higher levels of PI-9 than E2. In MCF7ERalphaHA cells, induction of high levels of PI-9 by both OHT and E2 inhibits TRAIL-mediated cytotoxicity. Our data suggest a new mechanism by which estrogen may contribute to the development of breast cancer. Furthermore, the powerful induction of PI-9 by OHT suggests a molecular mechanism to explain resistance to tamoxifen therapy in some of the often highly lethal breast cancers containing high levels of ER.","abstract_html":"To test the effect of estrogen receptor (ER) ligands that induce PI-9 on TRAIL-mediated cytotoxicity, we used MCF-7, human breast cancer cells. In MCF-7 cells, induction of PI-9 by 17beta-estradiol (E2) inhibited TRAIL-mediated cytotoxicity. This is the first demonstration that regulation of PI-9 expression from its endogenous promoter results in production of sufficient PI-9 to inhibit cytotoxocity by members of the TNF superfamily. To test the effect of the selective estrogen receptor modulator (SERM), 4-hydroxytamoxifen (OHT) (the active metabolite of tamoxifen), we used a tet-inducible MCF-7 cell model system, termed MCF7ERalphaHA cells. In MCF7ERalphaHA cells, OHT is a full agonist and induces higher levels of PI-9 than E2. In MCF7ERalphaHA cells, induction of high levels of PI-9 by both OHT and E2 inhibits TRAIL-mediated cytotoxicity. Our data suggest a new mechanism by which estrogen may contribute to the development of breast cancer. Furthermore, the powerful induction of PI-9 by OHT suggests a molecular mechanism to explain resistance to tamoxifen therapy in some of the often highly lethal breast cancers containing high levels of ER.","abstract_has_math":false,"creators":["Cunningham, Thomas D."],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":["Shapiro, David J."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-09-25T22:28:12Z","date_published":"2015-09-25T22:28:12Z","updated_at":"2026-07-22T22:26:24Z","subjects":["Biology, Cell"],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["(MiAaPQ)AAI3337746"],"render_values":[{"text":"(MiAaPQ)AAI3337746","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/84854","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Shapiro, David J."]},{"key":"dc:creator","label":"Author","values":["Cunningham, Thomas D."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2015-09-25T22:28:12Z","10000-01-01","2008"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"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, Cell"]}]},{"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/2142/84854","(MiAaPQ)AAI3337746"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["To test the effect of estrogen receptor (ER) ligands that induce PI-9 on TRAIL-mediated cytotoxicity, we used MCF-7, human breast cancer cells. In MCF-7 cells, induction of PI-9 by 17beta-estradiol (E2) inhibited TRAIL-mediated cytotoxicity. This is the first demonstration that regulation of PI-9 expression from its endogenous promoter results in production of sufficient PI-9 to inhibit cytotoxocity by members of the TNF superfamily. To test the effect of the selective estrogen receptor modulator (SERM), 4-hydroxytamoxifen (OHT) (the active metabolite of tamoxifen), we used a tet-inducible MCF-7 cell model system, termed MCF7ERalphaHA cells. In MCF7ERalphaHA cells, OHT is a full agonist and induces higher levels of PI-9 than E2. In MCF7ERalphaHA cells, induction of high levels of PI-9 by both OHT and E2 inhibits TRAIL-mediated cytotoxicity. Our data suggest a new mechanism by which estrogen may contribute to the development of breast cancer. Furthermore, the powerful induction of PI-9 by OHT suggests a molecular mechanism to explain resistance to tamoxifen therapy in some of the often highly lethal breast cancers containing high levels of ER.","Made available in DSpace on 2015-09-25T22:28:12Z (GMT). No. of bitstreams: 2 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 3337746.pdf: 1112153 bytes, checksum: 0184ee3aa66503e8d7f16b643abc1e03 (MD5) Previous issue date: 2008","Embargo set by: Seth Robbins for item 86135 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","81 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008."]},{"key":"dc:title","label":"Title","values":["Estrogen Inducible Proteinase Inhibitor 9 Protects Target Cells From Immune Surveillance and Apoptosis"]}]}],"canonical_facts":{"dc:contributor":["Shapiro, David J."],"dc:creator":["Cunningham, Thomas D."],"dc:date":["2015-09-25T22:28:12Z","10000-01-01","2008"],"dc:description":["To test the effect of estrogen receptor (ER) ligands that induce PI-9 on TRAIL-mediated cytotoxicity, we used MCF-7, human breast cancer cells. In MCF-7 cells, induction of PI-9 by 17beta-estradiol (E2) inhibited TRAIL-mediated cytotoxicity. This is the first demonstration that regulation of PI-9 expression from its endogenous promoter results in production of sufficient PI-9 to inhibit cytotoxocity by members of the TNF superfamily. To test the effect of the selective estrogen receptor modulator (SERM), 4-hydroxytamoxifen (OHT) (the active metabolite of tamoxifen), we used a tet-inducible MCF-7 cell model system, termed MCF7ERalphaHA cells. In MCF7ERalphaHA cells, OHT is a full agonist and induces higher levels of PI-9 than E2. In MCF7ERalphaHA cells, induction of high levels of PI-9 by both OHT and E2 inhibits TRAIL-mediated cytotoxicity. Our data suggest a new mechanism by which estrogen may contribute to the development of breast cancer. Furthermore, the powerful induction of PI-9 by OHT suggests a molecular mechanism to explain resistance to tamoxifen therapy in some of the often highly lethal breast cancers containing high levels of ER.","Made available in DSpace on 2015-09-25T22:28:12Z (GMT). No. of bitstreams: 2 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 3337746.pdf: 1112153 bytes, checksum: 0184ee3aa66503e8d7f16b643abc1e03 (MD5) Previous issue date: 2008","Embargo set by: Seth Robbins for item 86135 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","81 p.","Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008."],"dc:identifier":["http://hdl.handle.net/2142/84854","(MiAaPQ)AAI3337746"],"dc:language":["eng"],"dc:subject":["Biology, Cell"],"dc:title":["Estrogen Inducible Proteinase Inhibitor 9 Protects Target Cells From Immune Surveillance and Apoptosis"],"dc:type":["text"],"thesis:degree_discipline":["Biochemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:26:24Z"}