Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2025
Erindi/veggspjald / Talk/poster E74
Höfundar / Authors: Snædís Ragnarsdóttir (1), Laufey Tryggvadóttir (2), Linda Viðarsdóttir (3), Stefán Sigurðsson (3)
Starfsvettvangur / Affiliations: Háskóli Íslands
Kynnir / Presenter: Snædís Ragnarsdóttir
Background: While ER-positive (ER+) breast cancer (BC) typically carries a favorable prognosis, ER+ BRCA2 mutation carriers represent a high-risk subgroup with early metastasis and poor outcomes. The reason behind this unexpected outcome remains unclear. Methods: Using ER+ (MCF7) and ER− (MDA-MB-231) BC cell lines, we performed siRNA-mediated BRCA2 knockdown followed by estradiol (E2) treatment. DNA damage was assessed by 53BP1 foci immunofluorescence, micronucleus assays and metaphase spreads. Wound-healing assay was used to measure cell migration. Results: In ER+ cells, E2 significantly increased DNA damage in the context of BRCA2 loss, resulting in elevated 53BP1 foci, increased micronuclei and chromosomal aberrations. In contrast, ER− cells did not show comparable E2-driven DNA damage, highlighting a specific vulnerability of ER+ BRCA2-deficient cells. This genomic instability was accompanied by increased migratory ability. Wound-healing assays showed that siBRCA2-treated cells migrated faster than siControl cells and even faster when treated with E2. Conclusions: Our findings show that estradiol promotes genome instability and increases migratory traits in BRCA2-deficient ER+ BC, providing a mechanistic explanation for the poor outcomes seen in this patient group. These results emphasize the importance of considering estrogen-driven vulnerabilities when designing treatment strategies for BRCA2 mutation ER+ BC.