Chronic interferon-stimulated gene transcription promotes oncogene-induced breast cancer.

ABSTRACT: The MRE11 complex (comprising MRE11, RAD50, and NBS1) is integral to the maintenance of genome stability. We previously showed that a hypomorphic Mre11 mutant mouse strain (Mre11 ^ATLD1/ATLD1 ) was highly susceptible to oncogene-induced breast cancer. Here we used a mammary organoid system to examine which MRE11-dependent responses are tumor-suppressive. We found that Mre11 ^ATLD1/ATLD1 organoids exhibited an elevated interferon-stimulated gene (ISG) signature and sustained changes in chromatin accessibility. This Mre11 ^ATLD1/ATLD1 phenotype depended on DNA binding of a nuclear innate immune sensor, IFI205. Ablation of Ifi205 in Mre11 ^ATLD1/ATLD1 organoids restored baseline and o

SUBMITTER: Wang H 

PROVIDER: S-EPMC11610935 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature