Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.661900
Title: Mechanisms of transcriptional modulation of gene expression by oestrogen receptors
Author: Sierens, J.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2003
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Abstract:
The aims of this project were a) to determine whether ERβ WT and ERβ variant (ERβ2) forms exist in primates as well as in humans and to determine the ER localisation in reproductive tissues, b) to examine the localisation of GFP-tagged ER protein constructs (ERα, ERβ WT and ERβ2) within cells using a confocal microscope in the presence or absence of different oestrogenic ligands, c) to examine the functional dose response of ER proteins to different ligands using transient transfections in the presence of ERE-luciferase reporter constructs, d) to investigate an alternative activation mechanism for ERβ2 via a growth factor signalling pathway. RT-PCR results demonstrated that mRNA for ERβ WT and the ERβ2 variant were differentially expressed in tissues from the human, Old World (stump-tailed macaque) and New Word (common marmoset) primates. Immunohistochemical analysis resulted in detection of ERβ WT protein in both human and primate tissues but ERβ2 variant protein immunostaining was only positive in the human tissues. Sequence analysis revealed that the peptide used to raise the anti-ERβ2 antibody was not conserved in either primate. In human tissues, ERβ WT and ERβ2 had differential but overlapping patterns of expression so that formation of homo- or heterodimers might occur. In the absence of ligand the GFP-tagged ERs were diffusely distributed within the nucleus of transfected cells. Addition of oestrogenic ligands, induced rapid redistribution of the both ERα and ERβ WT receptors so that they adopted a ‘punctate’ nuclear pattern. The ERβ2 variant remained in a diffuse distribution throughout the nucleus even in the presence of ligand.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.661900  DOI: Not available
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