| Literature DB >> 27373334 |
Hua Wang1, Brian Bierie2, Andrew G Li3, Shailja Pathania3, Kimberly Toomire3, Stoil D Dimitrov4, Ben Liu3, Rebecca Gelman5, Anita Giobbie-Hurder5, Jean Feunteun6, Kornelia Polyak7, David M Livingston8.
Abstract
An abnormal differentiation state is common in BRCA1-deficient mammary epithelial cells, but the underlying mechanism is unclear. Here, we report a convergence between DNA repair and normal, cultured human mammary epithelial (HME) cell differentiation. Surprisingly, depleting BRCA1 or FANCD2 (Fanconi anemia [FA] proteins) or BRG1, a mSWI/SNF subunit, caused HME cells to undergo spontaneous epithelial-to-mesenchymal transition (EMT) and aberrant differentiation. This also occurred when wild-type HMEs were exposed to chemicals that generate DNA interstrand crosslinks (repaired by FA proteins), but not in response to double-strand breaks. Suppressed expression of ΔNP63 also occurred in each of these settings, an effect that links DNA damage to the aberrant differentiation outcome. Taken together with somatic breast cancer genome data, these results point to a breakdown in a BRCA/FA-mSWI/SNF-ΔNP63-mediated DNA repair and differentiation maintenance process in mammary epithelial cells that may contribute to sporadic breast cancer development.Entities:
Keywords: BRCA1; BRG1; EMT; FANCD2; breast cancer; cisplatin; crosslink repair
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Year: 2016 PMID： 27373334 PMCID： PMC4982517 DOI： 10.1016/j.molcel.2016.05.038
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970