{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/23537"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/23537","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Hormonal modulation of sex steroid hormone receptors and oncogenes in human breast cancer cells","abstract":"Since sex steroids modulate breast tumor growth, and high levels of the HER-2/neu protooncogene protein may contribute to breast cancer metastasis, the effects of estrogen, progestin and hormone antagonists on the levels of estrogen receptor (ER), progesterone receptor (PR) and HER-2/neu mRNA and protein have been studied in human breast cancer cell lines using cDNA and antibody probes. In all studies, protein response closely followed the RNA response. In MCF-7 cells, which contain high levels of ER and an estradiol (E$\\sb2$) induced PR, 1 nM E$\\sb2$ caused a 60% drop in ER mRNA (6.6 kb), a 10-fold rise in PR mRNA (5 species: 11.4, 5.8, 5.3, 3.5, 2.8 kb), and a 60% drop in HER-2neu mRNA levels (4.8 kb). These effects were dose-dependent (maximal effects $\\geq$ 10$\\sp{-10}$M), and were blocked by addition of excess antiestrogen. Treatment with the progestin R5020 (10 nM) partly reversed E$\\sb2$ effects on ER. R5020 and the antiprogestin RU486 (10 nM) both reduced PR mRNA levels by 50% but did not change HER-2/neu. In T47D cells, which contain low ER and high PR levels, E$\\sb2$ induced ER mRNA 2.5-fold in 2d. In contrast, R5020 reduced both ER mRNA and PR mRNA levels to 20% of control in 2d. RU486 caused an initial 50% drop by 6h followed by a rise to control levels by 48h. In T47D, no hormone studied changed HER-2/neu levels. Conclusions: (1) sex steroid hormones regulate their own receptors at the mRNA and protein levels, (2) progestin antagonizes E$\\sb2$ effects, (3) these E$\\sb2$ effects are mediated via ER (based on dose-dependence and antiestrogen antagonism), and (4) aggressiveness related to E$\\sb2$-treatment in MCF-7 cells is not associated with increased levels of HER-2/neu.","abstract_html":"Since sex steroids modulate breast tumor growth, and high levels of the HER-2/neu protooncogene protein may contribute to breast cancer metastasis, the effects of estrogen, progestin and hormone antagonists on the levels of estrogen receptor (ER), progesterone receptor (PR) and HER-2/neu mRNA and protein have been studied in human breast cancer cell lines using cDNA and antibody probes. In all studies, protein response closely followed the RNA response. In MCF-7 cells, which contain high levels of ER and an estradiol (E$\\sb2$) induced PR, 1 nM E$\\sb2$ caused a 60% drop in ER mRNA (6.6 kb), a 10-fold rise in PR mRNA (5 species: 11.4, 5.8, 5.3, 3.5, 2.8 kb), and a 60% drop in HER-2neu mRNA levels (4.8 kb). These effects were dose-dependent (maximal effects $\\geq$ 10$\\sp{-10}$M), and were blocked by addition of excess antiestrogen. Treatment with the progestin R5020 (10 nM) partly reversed E$\\sb2$ effects on ER. R5020 and the antiprogestin RU486 (10 nM) both reduced PR mRNA levels by 50% but did not change HER-2/neu. In T47D cells, which contain low ER and high PR levels, E$\\sb2$ induced ER mRNA 2.5-fold in 2d. In contrast, R5020 reduced both ER mRNA and PR mRNA levels to 20% of control in 2d. RU486 caused an initial 50% drop by 6h followed by a rise to control levels by 48h. In T47D, no hormone studied changed HER-2/neu levels. Conclusions: (1) sex steroid hormones regulate their own receptors at the mRNA and protein levels, (2) progestin antagonizes E$\\sb2$ effects, (3) these E$\\sb2$ effects are mediated via ER (based on dose-dependence and antiestrogen antagonism), and (4) aggressiveness related to E$\\sb2$-treatment in MCF-7 cells is not associated with increased levels of HER-2/neu.","abstract_has_math":true,"creators":["Read, Linnea Diane"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Biology, Molecular","degree_department":null,"school":null,"contributors":["Katzenellenbogen, Benita S."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-05-07T14:17:53Z","date_published":"2011-05-07T14:17:53Z","updated_at":"2026-07-22T22:25:22Z","subjects":["Biology, Molecular","Biology, Animal Physiology"],"languages":["eng"],"rights":["Copyright 1990 Read, Linnea Diane"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["AAI9114379","(UMI)AAI9114379"],"render_values":[{"text":"AAI9114379","href":null,"code":true},{"text":"(UMI)AAI9114379","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/23537","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Katzenellenbogen, Benita S."]},{"key":"dc:creator","label":"Author","values":["Read, Linnea Diane"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-05-07T14:17:53Z","10000-01-01","1990"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biology, Molecular","Biology, Animal 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, Molecular","Biology, Animal Physiology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 1990 Read, Linnea Diane"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["AAI9114379","(UMI)AAI9114379","http://hdl.handle.net/2142/23537"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Since sex steroids modulate breast tumor growth, and high levels of the HER-2/neu protooncogene protein may contribute to breast cancer metastasis, the effects of estrogen, progestin and hormone antagonists on the levels of estrogen receptor (ER), progesterone receptor (PR) and HER-2/neu mRNA and protein have been studied in human breast cancer cell lines using cDNA and antibody probes. In all studies, protein response closely followed the RNA response. In MCF-7 cells, which contain high levels of ER and an estradiol (E$\\sb2$) induced PR, 1 nM E$\\sb2$ caused a 60% drop in ER mRNA (6.6 kb), a 10-fold rise in PR mRNA (5 species: 11.4, 5.8, 5.3, 3.5, 2.8 kb), and a 60% drop in HER-2neu mRNA levels (4.8 kb). These effects were dose-dependent (maximal effects $\\geq$ 10$\\sp{-10}$M), and were blocked by addition of excess antiestrogen. Treatment with the progestin R5020 (10 nM) partly reversed E$\\sb2$ effects on ER. R5020 and the antiprogestin RU486 (10 nM) both reduced PR mRNA levels by 50% but did not change HER-2/neu. In T47D cells, which contain low ER and high PR levels, E$\\sb2$ induced ER mRNA 2.5-fold in 2d. In contrast, R5020 reduced both ER mRNA and PR mRNA levels to 20% of control in 2d. RU486 caused an initial 50% drop by 6h followed by a rise to control levels by 48h. In T47D, no hormone studied changed HER-2/neu levels. Conclusions: (1) sex steroid hormones regulate their own receptors at the mRNA and protein levels, (2) progestin antagonizes E$\\sb2$ effects, (3) these E$\\sb2$ effects are mediated via ER (based on dose-dependence and antiestrogen antagonism), and (4) aggressiveness related to E$\\sb2$-treatment in MCF-7 cells is not associated with increased levels of HER-2/neu.","Made available in DSpace on 2011-05-07T14:17:53Z (GMT). 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In all studies, protein response closely followed the RNA response. In MCF-7 cells, which contain high levels of ER and an estradiol (E$\\sb2$) induced PR, 1 nM E$\\sb2$ caused a 60% drop in ER mRNA (6.6 kb), a 10-fold rise in PR mRNA (5 species: 11.4, 5.8, 5.3, 3.5, 2.8 kb), and a 60% drop in HER-2neu mRNA levels (4.8 kb). These effects were dose-dependent (maximal effects $\\geq$ 10$\\sp{-10}$M), and were blocked by addition of excess antiestrogen. Treatment with the progestin R5020 (10 nM) partly reversed E$\\sb2$ effects on ER. R5020 and the antiprogestin RU486 (10 nM) both reduced PR mRNA levels by 50% but did not change HER-2/neu. In T47D cells, which contain low ER and high PR levels, E$\\sb2$ induced ER mRNA 2.5-fold in 2d. In contrast, R5020 reduced both ER mRNA and PR mRNA levels to 20% of control in 2d. RU486 caused an initial 50% drop by 6h followed by a rise to control levels by 48h. In T47D, no hormone studied changed HER-2/neu levels. Conclusions: (1) sex steroid hormones regulate their own receptors at the mRNA and protein levels, (2) progestin antagonizes E$\\sb2$ effects, (3) these E$\\sb2$ effects are mediated via ER (based on dose-dependence and antiestrogen antagonism), and (4) aggressiveness related to E$\\sb2$-treatment in MCF-7 cells is not associated with increased levels of HER-2/neu.","Made available in DSpace on 2011-05-07T14:17:53Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9114379.pdf: 4379295 bytes, checksum: b354e53aab50c1bbaa20147a1db6b004 (MD5) Previous issue date: 1990","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T15:05:09Z Item is restricted indefinitely.","Restriction data tranferred 2014-07-01T11:31:11-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission","ETDs are only available to UIUC Users without author permission","U of I Only"],"dc:identifier":["AAI9114379","(UMI)AAI9114379","http://hdl.handle.net/2142/23537"],"dc:language":["eng"],"dc:rights":["Copyright 1990 Read, Linnea Diane"],"dc:subject":["Biology, Molecular","Biology, Animal Physiology"],"dc:title":["Hormonal modulation of sex steroid hormone receptors and oncogenes in human breast cancer cells"],"dc:type":["text"],"thesis:degree_discipline":["Biology, Molecular","Biology, Animal Physiology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:25:22Z"}