Studies of Estrogen Receptor's Roles in Tamoxifen-Induced Apoptosis and the Regulation of Gene Expression

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biochemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Cheng, Jingwei

Contributors dc:contributor

• Shapiro, David J.

• Biology, Molecular

Language dc:language

eng

Identifier

(MiAaPQ)AAI3269858

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84839