Studies of Estrogen Receptor's Roles in Tamoxifen-Induced Apoptosis and the Regulation of Gene Expression
type: CreativeWork
description: Parallel work done by my colleague suggests that long-term activation of the ERK1/2 signal transduction pathway also plays an important role in OHT-induced apoptosis. To understand the connection between ERK1/2 activation and ER mediated gene expression, I chose serine 118 of ERalpha for further study. Serine 118 is a critical MAPK kinase phosphorylation site in ERalpha. To avoid potential artifacts due to transient transfection and use of artificial estrogen response element (ERE)-containing reporter genes, I isolated stably transfected cell lines that express the ERalphaS118A phosphorylation site mutant. Using stably transfected HeLa cell lines with functional ERK1/2 activity and expressing similar levels of wild-type ERalpha and ERalphaS118A, I compared expression of several classes of endogenous estrogen and tamoxifen-regulated genes. I concluded that phosphorylation of serine 118 is important for ER mediated gene transcription on some ERE-containing cellular genes while playing little role on other genes. Although estrogen and tamoxifen down-regulate numerous genes, mechanisms remain poorly understood. Interestingly, my data suggests a previously unknown requirement for serine 118 phosphorylation in estrogen and tamoxifen mediated gene down-regulation of gene expression.
abstract: Parallel work done by my colleague suggests that long-term activation of the ERK1/2 signal transduction pathway also plays an important role in OHT-induced apoptosis. To understand the connection between ERK1/2 activation and ER mediated gene expression, I chose serine 118 of ERalpha for further study. Serine 118 is a critical MAPK kinase phosphorylation site in ERalpha. To avoid potential artifacts due to transient transfection and use of artificial estrogen response element (ERE)-containing reporter genes, I isolated stably transfected cell lines that express the ERalphaS118A phosphorylation site mutant. Using stably transfected HeLa cell lines with functional ERK1/2 activity and expressing similar levels of wild-type ERalpha and ERalphaS118A, I compared expression of several classes of endogenous estrogen and tamoxifen-regulated genes. I concluded that phosphorylation of serine 118 is important for ER mediated gene transcription on some ERE-containing cellular genes while playing little role on other genes. Although estrogen and tamoxifen down-regulate numerous genes, mechanisms remain poorly understood. Interestingly, my data suggests a previously unknown requirement for serine 118 phosphorylation in estrogen and tamoxifen mediated gene down-regulation of gene expression.
author: Cheng, Jingwei
language: eng
keywords: Biology, Molecular
date published: 2015-09-25T22:28:09Z
date modified: 2026-07-22T22:26:24Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/84839