MassIVE MSV000087617

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Exposure to environmental chemicals alters human mammary gland morphogenesis and proteome

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Description

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. [doi:10.25345/C5NG07] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: mammary gland ; hormone signaling ; breast cancer ; environmental chemicals ; bisphenols ; organoids ; proteomics

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Principal Investigators:
(in alphabetical order) 		Susan Fisher, University of California San Francisco, United States of America
Submitting User: Sanrr
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