Cadmium Exposure Inhibits Branching Morphogenesis and Causes Alterations Consistent With HIF-1α Inhibition in Human Primary Breast Organoids.

ABSTRACT: Developmental cadmium exposure in vivo disrupts mammary gland differentiation, while exposure of breast cell lines to cadmium causes invasion consistent with the epithelial-mesenchymal transition (EMT). The effects of cadmium on normal human breast stem cells have not been measured. Here, we quantified the effects of cadmium exposure on reduction mammoplasty patient-derived breast stem cell proliferation and differentiation. Using the mammosphere assay and organoid formation in 3D hydrogels, we tested 2 physiologically relevant doses of cadmium, 0.25 and 2.5 µM, and tested for molecular alterations using RNA-seq. We functionally validated our RNA-seq findings with a hypoxia-inducible factor (HIF)-1α activity reporter line and pharmaceutical inhibition of HIF-1α in organoid formation assays

SUBMITTER: Rocco SA 

PROVIDER: S-EPMC6061678 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature