# Blockade of cMYC oncogenic function by pregnancy-induced alterations and remodeling of the mammary gland

> **NIH NIH R01** · COLD SPRING HARBOR LABORATORY · 2024 · $443,162

## Abstract

Abstract/Project Summary
The goal of this proposal is to understand how transitions through pregnancy influence the molecular and cellular
state of mammary epithelial cells and oncogenesis. Numerous epidemiological studies have found that
pregnancy alters the risk of breast cancer. These studies have shown consistently that a full-term pregnancy
prior to the age of 25 is associated with a one-third decrease in the life-time incidence of breast cancer. While a
protective effect of pregnancy has been validated in rodent models of cancer, the underlying molecular basis for
this effect remains unclear.
We have found that pregnancy leads to persistent changes in the epigenome and enhancer landscape of MECs.
Using an inducible c-MYC mouse model, we also find that oncogenesis and the transcriptional output
downstream of this oncogene are reduced in post-pregnancy MECs. In this proposal we will investigate the
molecular basis underlying these robust phenotypes. We will use epigenomics, ex vivo, in vivo and biochemical
methods to define how the transcriptional function of c-MYC is modulated by pregnancy. We hypothesize that c-
MYC interactions with cofactors and with specific cis-regulatory elements are altered in this system.
We will also study how specific chromatin regulators contribute to pregnancy-mediated epigenomic rewiring.
These efforts will build upon our recent data suggesting that EZH2 supports the post-pregnancy epigenome in
wild-type mice. Collectively, this research will provide fundamental insights into the cell biology of the mammary
gland and carry the potential for discoveries that could be harnessed to develop preventative treatments that
modulate breast cancer risk in humans.

## Key facts

- **NIH application ID:** 10915587
- **Project number:** 5R01CA284630-02
- **Recipient organization:** COLD SPRING HARBOR LABORATORY
- **Principal Investigator:** Camila dos Santos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $443,162
- **Award type:** 5
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10915587

## Citation

> US National Institutes of Health, RePORTER application 10915587, Blockade of cMYC oncogenic function by pregnancy-induced alterations and remodeling of the mammary gland (5R01CA284630-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10915587. Licensed CC0.

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