# Exploring the role of estrogen receptor beta in progression and metastasis ofInflammatory breast cancer

> **NIH NIH R01** · METHODIST HOSPITAL RESEARCH INSTITUTE · 2022 · $240,894

## Abstract

Abstract
Inflammatory breast cancer (IBC) is the most lethal form of breast cancer with median survival of about 4 years
compared with more than 10 years for other forms of breast cancer. Poor prognosis is associated with the high
propensity of these tumors to develop distant metastases. Despite a higher incidence of certain molecular
alterations in IBC, genetic profiling studies have failed to identify a specific therapeutic target and there are
currently no FDA-approved targeted therapies that are unique for the disease. The majority of IBC tumors lack
estrogen receptor α (ERα) suggesting the potential of ERβ to mediate effects of estrogen in these tumors.
Unlike the oncogenic ERα, ERβ is associated with epithelial differentiation and decreased invasion in non-IBC.
To investigate whether ERβ has a similar role in IBC, we analyzed human tumor tissues and datasets. Our
findings are the first to indicate expression of ER in more than 50% of IBCs and correlation of the receptor
with better survival. To investigate whether this association reflects the ability of ERβ to inhibit metastasis, we
studied preclinical models of IBC. Knockout of ER in IBC cells promotes through cytoskeleton remodeling
migration and activates molecules such as RhoC that are associated with cell motility and metastasis in IBC.
Conversely, ligands that activate ER potentiate its anti-migratory activity. Consistent with the in vitro anti-
migratory activity, ERβ proficient cells are less metastatic than ERβ knockout cells during preliminary analysis
of orthotopic and lung colonization models of IBC. We, therefore, hypothesize that ERβ and its agonists
prevent progression and metastasis of IBC tumors. Our proposed research will: 1) determine the role of ERβ
and its agonists in progression and metastasis of IBC, 2) elucidate the mechanism of the anti-metastatic
activity of ERβ and 3) examine whether ERβ is inversely associated with metastasis in IBC. To investigate the
role of ERβ in metastasis of IBC, we will examine how the receptor alters the metastatic potential of IBC cells
and tumors in vitro and in vivo. We will also evaluate the efficacy of ERβ ligands, that are currently in clinical
trials, to inhibit metastasis of IBC xenografts ensuring that our studies will impact the clinical treatment of IBC
(Aim 1). Further, we will delineate the molecular mechanisms of ERβ action by analyzing specific pathways
that are implicated in disease progression and metastasis (Aim 2). Finally, we will analyze clinical samples to
validate the expression of ERβ in tumors and verify its inverse association with metastasis (Aim 3). By defining
the role of ERβ and its associated pathways in progression and metastasis of IBC our research will provide
insights into the biology of IBC and assist to better understand why these tumors become metastatic. Our
study will also have important clinical implications by establishing ERβ as a novel and specific therapeutic
target that benefits patients w...

## Key facts

- **NIH application ID:** 10615449
- **Project number:** 7R01CA237200-04
- **Recipient organization:** METHODIST HOSPITAL RESEARCH INSTITUTE
- **Principal Investigator:** Christoforos Thomas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $240,894
- **Award type:** 7
- **Project period:** 2019-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10615449

## Citation

> US National Institutes of Health, RePORTER application 10615449, Exploring the role of estrogen receptor beta in progression and metastasis ofInflammatory breast cancer (7R01CA237200-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10615449. Licensed CC0.

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