# Estrogen receptor beta is a targetable melanoma tumor suppressor

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $356,359

## Abstract

PROJECT SUMMARY/ABSTRACT
Melanoma is more prevalent in men than women, suggesting sex hormones may influence this disease. Clinical
studies correlate decreased estrogen receptor beta (ERβ) expression with disease progression. However, the
mechanisms by which the receptor protects against melanoma formation and progression remain unknown.
Our preliminary data show that ERβ loss accelerates tumor formation in a murine melanoma model thereby
confirming the tumor suppressor activity implicated in the clinical data. The melanocyte ERβ cistrome overlaps
with key melanocyte transcription factors that act as master regulators of differentiation, proliferation, and
migration. Estrogen-regulated genes in melanocytes are associated with differentiation and migration pathways
supporting a co-regulatory link between ERβ and these master regulators.
In addition to the tumor suppressor function of ERβ in melanocytes, ERβ has a melanocyte-nonautonomous
function that results in reduced immune infiltrates within the tumor. Furthermore, an ERβ-specific agonist can
activate T cells, reduce immune checkpoint inhibitor expression, and increase T cell activation.
These data lead to the overarching hypothesis that ERβ activity represses melanoma initiation and
progression by modulating melanocyte-intrinsic master regulator activity and enhancing immune
responses to the tumor. In this proposal, the hypothesis will be tested by 1) Defining the melanocyte-intrinsic
ERβ activities that repress melanoma onset and progression; 2) Determining the influence of ERβ-regulated
immune activities on melanoma initiation and therapeutic response.

## Key facts

- **NIH application ID:** 10365404
- **Project number:** 1R01CA255158-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Craig J Burd
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $356,359
- **Award type:** 1
- **Project period:** 2021-12-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10365404

## Citation

> US National Institutes of Health, RePORTER application 10365404, Estrogen receptor beta is a targetable melanoma tumor suppressor (1R01CA255158-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10365404. Licensed CC0.

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