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Exposure to environmental chemicals alters human mammary gland morphogenesis and proteome

ABSTRACT: Environmental chemicals such as bisphenol A (BPA) are thought to contribute to carcinogenesis through their endocrine-disrupting effects. However BPA replacement chemicals are structurally similar, and little data exist describing their effects on the human body and environment. We established non-malignant human mammary organoid cultures to investigate the effects of BPA replacement chemicals on organoid morphology and protein abundance. At low-nanomolar doses, replacement chemicals, in particular BPS, induced branching and disrupted the organized mammary organoid architecture. BPS exposure likely alters mammary cell-type proportions and induces branching of predominately myoepithelial cells. Treatment with different replacement chemicals resulted in distinct proteomic changes. BPS exposure induced Cdc42-interacting protein 4 (CIP4), a protein known to support invadopodia formation and mesenchymal phenotypes. Our study provides evidence that replacement bisphenols have pro-tumorigenic effects on mammary morphology and the proteome, highlighting the necessity of comprehensive studies to evaluate the potential harm of replacement chemicals.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Susan Fisher

PROVIDER: MSV000087617 | MassIVE | Fri Jun 11 15:48:00 BST 2021

REPOSITORIES: MassIVE

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