Files in this item



application/pdf3392443.pdf (1MB)Restricted to U of Illinois
(no description provided)PDF


Title:A Novel Link Between Oxidative Stress Proteins and Estrogen Receptor Alpha-Mediated Gene Expression
Author(s):Rao, Abhilasha
Doctoral Committee Chair(s):Katzenellenbogen, Benita S.; Nardulli, Ann M.
Department / Program:Cell and Developmental Biology
Discipline:Cell and Developmental Biology
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Biology, Molecular
Biology, Physiology
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.
Issue Date:2009
Description:68 p.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2009.
Other Identifier(s):(UMI)AAI3392443
Date Available in IDEALS:2014-12-17
Date Deposited:2009

This item appears in the following Collection(s)

Item Statistics