# Estrogen and glucocorticoid receptor crosstalk in ER+ breast

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $334,705

## Abstract

PROJECT ABSTRACT
Approximately 70% of invasive breast cancer expresses estrogen receptor-alpha (ER). Our lab and others
have found that 50-60% of early-stage ER+ breast cancers also express glucocorticoid receptor (GR), and that
high GR expression provides favorable prognostic information in early-stage breast cancer independently of
PR expression. Specifically, in an analysis of primary tumor GR expression in ER+ invasive breast tumors from
over 1000 ER+ early-stage patients with >20 year clinical follow-up, we discovered that high tumor GR mRNA
expression (and by implication, high GR activity) was associated with a significantly lower risk of relapse. More
recently, we found that in ER+ breast cancer cell line models, GR activation remodels chromatin so that ER-
chromatin association and ER-target gene expression are significantly altered. Based on these data, we
hypothesize that ER and GR can provide coordinated regulation of good prognosis, anti-proliferative and pro-
differentiation genes. We propose to determine the molecular mechanisms underlying GR-mediated
modulation of both wild-type and mutant ER transcriptional activity, and to define the specific patterns of
ER/GR-mediated gene expression in breast cancer. In Aim 1, we will characterize how GR ligand binding
domain activation [by either dexamethasone (dex) or novel selective GR modulators (SGRMs)] affects ER
activity, consequent ER-mediated gene expression, and ultimately ER-associated tumor cell proliferation. In
Aim 2, we will investigate GR and ER chromatin and co-regulator association in the presence of dex in
comparison to the novel SGRMs. This will allow us to better understand the requirements of chromatin
conformation and GR/ER co-regulator assembly in modifying ER+ breast cancer's proliferative gene
expression. Finally, in Aim 3, we will use in vivo ER+ breast cancer patient-derived xenograft models, mutant
ER-expressing cell lines, and tamoxifen-resistant ER+ models to define SGRM anti-tumor activity with the aim
of defining clinical contexts in which GR modulators are most likely to be effective. Together, these
experiments will both increase our understanding of GR/ER crosstalk in breast cancer (and possibly other
hormone-sensitive cancers e.g. endometrial) and are expected to lead to new GR-targeted therapies that
harness our discovery of anti-proliferative activity following GR modulation in ER+/GR+ breast cancer.

## Key facts

- **NIH application ID:** 9873001
- **Project number:** 7R01CA238519-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Suzanne Daniela Conzen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $334,705
- **Award type:** 7
- **Project period:** 2019-03-01 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873001

## Citation

> US National Institutes of Health, RePORTER application 9873001, Estrogen and glucocorticoid receptor crosstalk in ER+ breast (7R01CA238519-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9873001. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*