# Adelaide University: DNA enhancer HRR INT3 helps androgen receptor restrain ER+ breast cancer cells

- Published: 2026-11-06 01:43 UTC
- Section: Life & Health › Medicine
- Tags: HRR INT3 enhancer, androgen receptor, ER-positive breast cancer, ZBTB16 gene, CRISPR/Cas9 deletion, tumour suppression, H3K27ac, E2F targets, npj Breast Cancer
- URL: https://realtech.media/news/rt-35806413ca1395486854bcdc_adelaide_university_dna/

**In breast and prostate cancer cell models, deleting the HRR INT3 enhancer weakened androgen receptor growth suppression, while changing ZBTB16 levels alone did not.**

![Adelaide University: DNA enhancer HRR INT3 helps androgen receptor restrain ER+ breast cancer cells](https://sgzwpqqelzmajkcubgkl.supabase.co/storage/v1/object/public/rt-media/2026/11/fec2dfa9fd7920ea.jpg)
*Mateus Figueiredo, Wikimedia Commons, CC BY 4.0*

Researchers at Adelaide University's School of Medicine, the South Australian immunoGENomics Cancer Institute (SAiGENCI) and SAHMRI, together with colleagues at the University of Bordeaux, identified a regulatory DNA region that supports the tumour-suppressor activity of the androgen receptor (AR) in oestrogen receptor-positive (ER⁺) breast cancer. The work, done in cell models and clinical specimens, was published in npj Breast Cancer [1]. According to the university's release, up to 80% of breast cancers are ER⁺.

## ZBTB16 expression and the androgen receptor

The AR represses cell cycle genes and restrains proliferation in ER⁺ breast cancer. The team had earlier proposed ZBTB16 as a candidate gene regulated by the AR. In clinical cohorts, ZBTB16 mRNA was lower in breast tumours than in normal tissue, and higher expression correlated with better survival in ER⁺ disease [1]. Androgen treatment raised ZBTB16 protein in ER⁺ breast cancer cell lines [1].

However, knockdown or overexpression of ZBTB16 did not detectably change the anti-proliferative effect of the AR in the models tested [1]. "The surprising finding was that ZBTB16 itself was not responsible for the growth-suppressing effect," said Dr Amy Dwyer of Adelaide University.

## The HRR INT3 enhancer

The AR bound a conserved hormone response region in intron 3 of the ZBTB16 locus, named HRR INT3, in breast cancer models and clinical specimens. Binding was accompanied by androgen-dependent H3K27ac enrichment, consistent with an AR-responsive enhancer [1].

Using CRISPR/Cas9, the researchers deleted HRR INT3. The deletion prevented AR-dependent induction of ZBTB16, impaired AR-mediated growth suppression and attenuated activation of canonical AR target genes [1]. Baseline proliferation increased in breast and prostate cancer cells, with upregulation of E2F targets [1]. The authors describe HRR INT3 as a lineage-conserved enhancer contributing to AR-mediated tumour suppression across AR⁺ cancers [1].

"This tells us that the enhancer is doing much more than simply controlling ZBTB16," said co-author Dr Zeyad Nassar of SAiGENCI and SAHMRI. The researchers note that treatments activating the AR are already being investigated for advanced ER⁺ breast cancer, and say that understanding the molecular machinery behind the effect is important.

## Sources

1. [npj Breast Cancer](https://doi.org/10.1038/s41523-026-01037-5)
2. [newswise.com](https://www.newswise.com/articles/dna-switch-uncovers-new-brake-on-breast-cancer-growth)

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Source: RealTech, realtech.media — https://realtech.media/news/rt-35806413ca1395486854bcdc_adelaide_university_dna/