Estrogen Receptor Beta: Impact of Ligands on

Intracellular Shuttling and

Turnover Rate in Breast Cancer Cells

A research proposal under the course of “Research Project Development”

Course Code: BIO-409

Proposal preparedby
Tasnim Islam Prianka

Roll: 19 BIO 019

Year: Fourth (4th)

Proposal submitted to
Dr. Rehana Parvin

Associate Professor &Chairman

Department of Biochemistry and Biotechnology

University of Barishal
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Content Table

Content Page
Abstract
Introduction
Objective
Required Materials
and Possible Methods
Expected Results
Discussion
Conclusion
References
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Abstract: Estrogen receptor is a member of a superfamily of hormone-regulated transcription

factors that stimulate gene expression in response to estrogens. The ability to switch ER functions
from inactive to active state by simply adding ligand has illuminated several fundamental insights
into eukaryotic transcriptional regulation. Some of these ligands show agonistic or antagonistic
effects depending on ER subtype and are described as selective ER modulators. Impact of the beta
isoform of estrogen receptor (ER) on breast cancer etiology and progression is now well
established. Data accumulated during the last four years on the mechanism of action of ER enable
one to foresee new strategies. These data indeed reveal that ER is not statically bound to DNA at
promoter sites of genes regulating cell proliferation and differentiation but rather behaves as a
very mobile protein continuously shuttling between targets. ER into MCF-7 cells causes an
inhibition of proliferation in vitro and prevents tumor formation in a mouse xenograft model in
response to estradiol. Changes in ER turnover rate associated with these regulatory processes
seem also to strongly influence the ability of the receptor to mediate gene transactivation.

Introduction: Estrogen, a steroid compound, is primarily produced by the ovaries and placenta
in females. The adrenal cortex of males also produce estrogen. Estrogens play important
modulatory roles in physiological and pathophysiological processes. The estrogen receptors, ERα,
ERβ, and GPER, mediate the effects of estrogenic compounds on their target tissues. ERβ
expression is an independent prognostic marker in ERα+-progesterone receptor positive breast
cancer. Estrogen is essential for normal growth and differentiation in the mammary gland. It also
supports growth of approximately 50% of primary breast cancers. The presence of ER
beta significantly reduced both primary tumor growth and metastasis. Many nuclear receptors are
activated by specific ligands and generally act as transcription factors by binding to specific DNA
sequences in the genome.
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