# Mechanism of Tumor Suppressor Function of Progesterone Receptor in Breast Cancer

> **NIH NIH P20** · UNIVERSITY OF NORTH DAKOTA · 2020 · $178,097

## Abstract

Project Summary:
Breast cancer is the second leading cause of cancer death in women in the U.S. In 2020, about 276,000 new
cases of invasive breast cancer are expected to be diagnosed in women in the United States. Steroid hormone
receptors, estrogen receptor (ER) and progesterone receptor (PR), are critical for normal breast tissue
development as well as breast tumor development. The majority of breast cancers (~70%) express those
hormone receptors. Function of ER in breast cancer has been extensively studied and ER-targeting therapy such
as tamoxifen is routinely used for ER-positive breast cancers. However, acquisition of resistance to anti-ER
therapies in breast cancers constitutes a major obstacle to successful treatments. Therefore, there is an urgent
need to develop a new therapeutic strategy. Surprisingly, in contrast to ER, PR function in breast cancer is not
well-studied. Progesterone (a ligand of PR) is known to inhibit ER and PR positive breast cancer growth in vitro
and in vivo. Importantly, progesterone is also known to facilitate breast cancer cell cycle and increase breast
cancer risk Although progesterone treatment has been considered as a promising breast cancer treatment,
because of this bipolar function of PR in breast cancer and our lack of knowledge for the molecular mechanism
of PR action, the clinical significance of progesterone treatment is still obscure. Particularly, the mechanism of
PR-mediated cell cycle regulation remains elusive. In this proposal, we aim to identify the mechanism of
progesterone-induced cell cycle arrest in breast cancer cells. Our central hypothesis is that PR regulate cell cycle
regulatory miRNAs by forming chromatin loops (3D interaction) between PR bound enhancers and miRNA-
coding loci. The central hypothesis will be tested by pursuing three specific aims: (1) Identify cell cycle gene
targeting miRNAs activated by PR; (2) Define the role of chromatin loop formation induced by PR; (3) Determine
the impact of PR reactivation in PR deficient breast cancer cells. We will utilize the innovative combination of
techniques - an advanced genomic technique (HiChIP), CRISPR-mediated knockout, and our PR impaired
breast cancer cell line to identify progesterone-induced miRNAs that regulate breast cancer cell proliferation.
The proposed research is significant because it is expected to contribute a missing and fundamental element to
our understanding of the role of PR in breast cancer growth. Ultimately, such knowledge has the potential to
offer development of new therapeutic strategies of breast cancer treatment. Characterized miRNAs in this study
also have potential to be used as biomarkers for progesterone-treatable breast cancers.

## Key facts

- **NIH application ID:** 10154116
- **Project number:** 3P20GM104360-07S1
- **Recipient organization:** UNIVERSITY OF NORTH DAKOTA
- **Principal Investigator:** ROXANNE A VAUGHAN
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $178,097
- **Award type:** 3
- **Project period:** 2013-09-10 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10154116

## Citation

> US National Institutes of Health, RePORTER application 10154116, Mechanism of Tumor Suppressor Function of Progesterone Receptor in Breast Cancer (3P20GM104360-07S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10154116. Licensed CC0.

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