Evidence for accelerated aging in mammary epithelia of women carrying germline BRCA1 or BRCA2 mutations.

ABSTRACT: During aging in the human mammary gland, luminal epithelial cells lose lineage fidelity by expressing markers normally expressed in myoepithelial cells. We hypothesize that loss of lineage fidelity is a general manifestation of epithelia that are susceptible to cancer initiation. In the present study, we show that histologically normal breast tissue from younger women who are susceptible to breast cancer, as a result of harboring a germline mutation in BRCA1, BRCA2 or PALB2 genes, exhibits hallmarks of accelerated aging. These include proportionately increased luminal epithelial cells that acquired myoepithelial markers, decreased proportions of myoepithelial cells and a basal differentiation bias or failure of differentiation of cKit⁺ progenitors. High-risk

SUBMITTER: Shalabi SF 

PROVIDER: S-EPMC8849557 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature