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Updated: Jul 12, 2025

Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
Chronic Interferon Stimulated Gene Transcription Promotes Oncogene Induced Breast Cancer
The Mre11 complex is crucial for genome stability. Its deficiency in mammary organoids triggers innate immune responses, suppressing tumor formation and metastasis.
Area of Science:
- Genetics
- Immunology
- Cancer Biology
Background:
- The Mre11 complex (Mre11, Rad50, Nbs1) maintains genome stability.
- A hypomorphic Mre11 mutant mouse strain is susceptible to oncogene-induced breast cancer.
Approach:
- Utilized a mammary organoid system to investigate Mre11-dependent tumor suppressive responses.
- Examined the role of the innate immune sensor IFI205 in Mre11-deficient organoids.
Key Points:
- Mre11-deficient organoids show an elevated interferon-stimulated gene (ISG) signature and altered chromatin accessibility.
- This phenotype is dependent on IFI205 DNA binding.
- Ablating IFI205 in Mre11-deficient organoids normalized chromatin accessibility.
- Mre11-deficient organoids promoted aggressive metastatic breast cancer, an effect reversed by IFI205 ablation.
Conclusions:
- Revealed a link between innate immune signaling and tumor suppression in mammary epithelium.
- Suggests that cancer predisposition in genome instability syndromes may involve tonic innate immune transcriptional programs.
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