Iron-catalyzed oxidative stress compromises cancer promotional effect of BRCA2 haploinsufficiency through mitochondria-targeted ferroptosis.

ABSTRACT: Pathogenic variants in BRCA2 are hereditary risks for various cancers, including breast, ovary, pancreas and prostate. Genomic instability due to insufficient homologous recombination is thought as responsible for carcinogenesis. Reportedly, endogenous or exogenous aldehydes, including formaldehyde and acetaldehyde, suppress BRCA2 function. However, molecular sequences how BRCA2 insufficiency leads to carcinogenesis remains unelucidated. To assess whether Fenton reaction-based oxidative stress is a promotional risk factor of carcinogenesis in BRCA2 haploinsufficiency, we here applied iron-induced renal carcinogenesis to a newly established rat heterozygous mutation model of Brca2 (mutant, T1942Kfs/+; MUT). Rat MUT model, despite significant increase in spontaneous malignant tumors, showed

SUBMITTER: Maeda Y 

PROVIDER: S-EPMC12270739 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature