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Ligand- and Phosphorylation-dependent Modulation of Estrogen Reeptor Target Gene Expression

by Koterba, Kristen L.

Abstract (Summary)
17"?"-estradiol (E2) has a central role in the proliferation of estrogen responsive cells through the modulation of target gene expression within estrogen responsive tissues. The effects of E2 are mediated through binding to the Estrogen Receptor "?" nuclear receptor transcription factor. Tamoxifen also binds to the estrogen receptor to modulate ER-mediated gene transcription. Although tamoxifen is an antiestrogen in breast tissue, it also contains partial estrogenic activity in the uterus and is associated with an increased risk of developing uterine cancer. Tamoxifen can act as an ER antagonist, inducing a conformational change in the receptor that blocks its interaction with coactivators. This study has employed a novel methodology specifically called bioluminescent resonance energy transfer (BRET2) to accurately measure protein-protein interactions. Understanding the roles of ER"?" and coregulators in a ligand-independent and dependent manner may elucidate a mechanism in the tissue selectivity of tamoxifen that has not yet been determined.
Bibliographical Information:

Advisor:

School:University of Toledo Health Science Campus

School Location:USA - Ohio

Source Type:Master's Thesis

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ISBN:

Date of Publication:01/01/2006

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