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?

xlomafota13 shared this article with you from Inoreader 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? Via American Journal of Cancer Research Am J Cancer Res. 2021 Jun 15;11(6):3263-3270. eCollection 2021. 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 notion that reduced Foxa1 expression is sufficient to alter mammary g land luminal cell fate determination in vivo, which could be a mechanism linking parity with ER- breast cancer. PMID:34249460 | PMC:PMC8263678 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.