# Expression of endogenous retroviral elements is associated with extracellular matrix remodeling in prostate cancer

## TL;DR

This study shows that deleting Trim28 in prostate cancer leads to increased retroviral expression, which affects nearby genes and tumor matrix changes.

## Contribution

The study reveals a novel link between Trim28 deletion, ERV activation, and extracellular matrix remodeling in prostate cancer.

## Key findings

- Trim28 deletion in prostate tumors leads to ERV expression in both hormonally intact and castrated mice.
- Increased expression of protein-coding genes near overexpressed ERVs was observed.
- Trim28 deletion caused excessive extracellular matrix deposition in prostate tumors.

## Abstract

How endogenous retroviral elements (ERVs), a family of transposable elements, may promote tumor progression is not well understood. Tripartite motif-containing 28 (TRIM28/TIF1b/KAP1) is a key transcriptional co-repressor protein that represses ERV expression in many cell types including embryonic stem cells, neural progenitor cells, differentiated adult cells, and cancer cells. In this study, we investigated the effect of Trim28 deletion on the expression of ERVs using an immune competent genetically engineered mouse model for prostate cancer. We found Trim28 deletion in prostate tumors led to the expression of ERVs in prostates from both hormonally intact and castrated mice. ERVs can regulate the expression of neighboring genes, and we detected increased expression of several protein-coding genes near overexpressed ERVs. Our data suggest that Trim28 deletion in prostate tumor epithelial cells may promote an innate immune response. However, Trim28 deletion also led to excessive deposition of tumor extracellular matrix (ECM). Our findings suggest that ECM alterations downstream of ERV derepression could affect immune cells in the tumor microenvironment and may promote tumor progression.

The online version contains supplementary material available at 10.1186/s13100-025-00382-9.