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Title:Estrogen Inducible Proteinase Inhibitor 9 Protects Target Cells From Immune Surveillance and Apoptosis
Author(s):Cunningham, Thomas D.
Doctoral Committee Chair(s):Shapiro, David J.
Department / Program:Biochemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Biology, Cell
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.
Issue Date:2008
Description:81 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2008.
Other Identifier(s):(MiAaPQ)AAI3337746
Date Available in IDEALS:2015-09-25
Date Deposited:2008

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