Deletion of Foxa1 in the mouse mammary gland results in abnormal accumulation of luminal progenitor cells: a link between reproductive factors and ER-/TNBC breast cancer?

ABSTRACT: In humans, parity without breastfeeding increases risk of estrogen receptor-negative (ER-) breast cancer and is associated with hypermethylation of FOXA1, a pioneer factor regulating lineage commitment of mammary gland luminal progenitor cells. We postulate that pregnancy-associated repression of FOXA1 results in the accumulation of aberrant, differentiation-arrested luminal progenitor cells which, following additional genetic and epigenetic insults, may give rise to ER- tumors. Consistent with this hypothesis, we show that deletion of Foxa1 in the mouse mammary gland results in a two-fold increase in the proportion of luminal progenitor cells and a reduction in mammary gland epithelial cells that stain positive for ER. These results provide compelling support for the

SUBMITTER: Sribenja S 

PROVIDER: S-EPMC8263678 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature