# Repressive Transcriptional Programs in Breast Cancer

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $148,413

## Abstract

ABSTRACT
We propose a study of functional interactions between nuclear receptors in breast cancer cells as a project
under this USA-NFSC initiative, with great scientific and intellectual benefit, based on the efforts of two closely-
collaborating investigators with shared research interests, but with disparate areas of expertise. Drs. Michael
Rosenfeld and Wen Liu have an extensive history of effective collaborations, as evidenced in a number of
fundamental discoveries over the past ten years, including nine co-authored papers. This project, involving a
sustained, close scientific interaction and collaboration is based on their complementary expertise, focus and
resources. We propose to establish an unappreciated, but critical, molecular strategy that serves as the basis
for large enhancer-dependent programs of coding target gene transcriptional repression important in breast
cancer. This program depends on the fact that ERα is recruited in trans to the basally active enhancers that
mediate the repressive transcriptional program, with trans-bound ERα receptor recruiting a demethylase,
based on the availability of its DNA binding domain, which in turn recruits machinery leading to dismissal of Pol
II from these basally highly active enhancers, causing their repression. This mechanism therefore represents a
previously unappreciated type of repressive strategy, and involves a gene set that serves as a powerful
prognostic indicator of a ten-year metastasis-free survival. This would uncover a set of largely overlooked
prognostic biomarkers for breast cancer patients, perhaps ultimately providing a potential target for treatment
or prevention of aggressive breast cancers. A strategy is proposed to underlie the ability of liganded
glucocorticoid receptor to inhibit the ERα-activated regulatory enhancers in breast cancer cells, based on
competition between different members of the nuclear receptor family.

## Key facts

- **NIH application ID:** 9830606
- **Project number:** 5R01CA213371-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** MICHAEL G ROSENFELD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $148,413
- **Award type:** 5
- **Project period:** 2016-12-13 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830606

## Citation

> US National Institutes of Health, RePORTER application 9830606, Repressive Transcriptional Programs in Breast Cancer (5R01CA213371-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9830606. Licensed CC0.

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