# The roles of TRIM24 in breast cancer

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2020 · $402,021

## Abstract

PROJECT SUMMARY
Breast cancer is a deadly disease and new strategies are needed to fulfill the goals of treatment and
eradication. Recent development of epigenetic-based inhibitors offers new avenues of potential therapeutics
for breast and other human cancers. Our work using a new mouse model of breast cancer that parallels the
aberrant expression of TRIM24 in all breast cancer sub-types will be used to gain a deeper understanding of
tumor development and treatment. Epigenetic regulators are frequent targets of aberrant regulation,
amplification or mutation in all human cancers. Histone “writers”, “erasers” and “readers” are epigenetic
regulators that catalyze addition, removal and/or interaction, respectively, with post-translational modifications
(PTMs) of histones or other modified proteins, with subsequent regulatory outcomes for gene expression. Our
laboratory discovered Tripartite Motif Protein 24 (TRIM24) as a histone reader and showed that TRIM24: (i)
ubiquitinated p53 and siRNA-depletion of TRIM24 led to p53-dependent apoptosis of embryonic stem cells and
breast cancer-derived cells (MCF7), (ii) recruited estrogen receptor to chromatin by PHD/bromodomain reading
of a unique signature of histone PTMs (H3K4me0; H3K23ac) to co-regulate estrogen-dependent transcription,
(iii) induced transformation of immortalized human mammary epithelial cells (iHMECs) by altering metabolism
and up-regulating c-Myc expression when ectopically expressed, and (iv) a small molecule inhibitor of the
TRIM24 bromodomain disrupts chromatin interactions in vitro. Importantly, we found that aberrant expression
of TRIM24 negatively correlates with breast cancer patient survival. TRIM24 is over expressed in all sub-types
of breast cancer and is highest in basal breast cancers. We developed a mouse model of TRIM24-expressing
breast cancers by conditional over-expression of a Trim24 transgene in mammary epithelia. We saw that
aberrant, tissue-specific expression of TRIM24 is sufficient for tumor initiation, development and progression to
highly heterogeneous mammary carcinomas. We hypothesize that our proposed, multi-faceted studies,
including mouse models, cultured cells and in vitro analyses will uncover how aberrant expression of TRIM24
drives heterogeneous tumor development in mammary/breast epithelia, and that our findings will further
development of epigenetic-based therapeutics to treat breast cancers. Our long-term goal is to leverage a
deep mechanistic understanding of TRIM24 functions toward innovative therapeutic approaches to treat breast
and other cancers in humans.

## Key facts

- **NIH application ID:** 9868916
- **Project number:** 5R01CA214871-04
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** GUILLERMINA LOZANO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,021
- **Award type:** 5
- **Project period:** 2017-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868916

## Citation

> US National Institutes of Health, RePORTER application 9868916, The roles of TRIM24 in breast cancer (5R01CA214871-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9868916. Licensed CC0.

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