Investigation of the mechanisms of estrogen receptor activation by phosphorylation

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Title: Investigation of the mechanisms of estrogen receptor activation by phosphorylation
Authors: Halliday, Amy Catherine
Item Type: Thesis or dissertation
Abstract: Breast cancer growth is estrogen- regulated in many cases. Estrogen actions are mediated by estrogen receptors ERα and ERβ. Whilst the involvement of ERβ in breast cancer is unresolved at present, up to 80% of breast tumours are ERα- positive and likely to respond to endocrine therapies, such as anti-estrogens. However, a substantial proportion of patients develop a resistance to such treatments. Most resistant tumours continue to express ERα and many will respond to an alternative hormonal therapy, indicating that ERα continues to be important following the emergence of resistance. One proposed mechanism for endocrine resistance is post-translational modification of the ERα, particularly phosphorylation of ERα within the transcription activation domain AF1. This project investigates how the phosphorylation at residues within the AF1 domain is linked to ERα activation and tumour cell growth in the presence of tamoxifen and in the absence of ligand, by stable introduction of ERα phosphorylation site mutants in the MCF7 human breast cancer cell line, commonly used as a model for ERα-positive breast cancer. Characterisation of these lines suggests that phosphorylation at the sites within the AF1 domain of the ER increases the agonist activity of tamoxifen. Further studies to determine the mechanisms by which ERα activity is regulated by phosphorylation within AF1 are discussed.
Issue Date: Mar-2009
Date Awarded: Mar-2009
Supervisor: Ali, Simak
Author: Halliday, Amy Catherine
Department: Division of Surgery, Oncology, Reproductive Biology and Anaesthetics (SORA)
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Medicine PhD theses

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