A Multistage Murine Breast Cancer Model Reveals Long-Lived Premalignant Clones Refractory to Parity-Induced Protection.

ABSTRACT: Breast cancers evolve in a multistage process that can span decades after a carcinogenic exposure. It follows that long-lived precursor breast lesions persist in a subclinical state prior to completing malignant transformation, yet widely used breast cancer models lack an experimental framework for targeting premalignant disease. Inspired by classic multistage skin carcinogenesis protocols, we combined chemical carcinogenesis with transgenic mouse modeling to resolve mouse mammary carcinogenesis into discrete initiation and progression stages. At the initiation stage, exposure to the carcinogen 7,12-dimethylbenzanthracene (DMBA) generated "initiated mammary epithelial cells" (iMEC) by introducing a stereotyped Hras^Q61L driver mutation. Whether DMBA exposure occurred durin

SUBMITTER: Li S 

PROVIDER: S-EPMC7007345 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature