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

112 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2007.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.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD