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Bisphenol A replacement chemicals, BPF and BPS, induce protumorigenic changes in human mammary gland organoid morphology and proteome

Permanent link
https://hdl.handle.net/10037/25979
DOI
https://doi.org/10.1073/pnas.2115308119
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Date
2022-03-09
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Author
Winkler, Juliane; Liu, Pengyuan; Phong, Kiet; Hinrichs, Johanna H.; Ataii, Nassim; Williams, Katherine; Hadler-Olsen, Elin Synnøve; Samson, Susan; Gartner, Zev J.; Fisher, Susan; Werb, Zena
Abstract
Environmental chemicals such as bisphenol A (BPA) are thought to contribute to carcinogenesis through their endocrine-disrupting properties. Due to accumulating evidence about negative human health effects, BPA is being phased out, but in parallel, exposures to replacement chemicals such as bisphenol S (BPS) and bisphenol F (BPF) are increasing. Little is known about their biologic effects, but because of their high degree of chemical relatedness, they may have overlapping as well as distinct actions as compared with BPA. We investigated this theory using a nonmalignant, human breast tissue-derived organoid system and two end points: morphologic and proteomic alterations. At low-nanomolar doses, replacement chemicals—particularly BPS—disrupted normal mammary organoid architecture and led to an increased branching phenotype. Treatment with the various bisphenols (vs. 17-β-estradiol or a vehicle control) produced distinct proteomic changes. For example, BPS up-regulated Cdc42-interacting protein 4, which supports the formation of invadopodia and a mesenchymal phenotype. In summary, this study used a highly physiologically relevant organoid system to provide evidence that replacement bisphenols have protumorigenic effects on the mammary gland at morphologic and proteomic levels, highlighting the importance of studies to evaluate the potential harmful effects of structurally related environmental chemicals.
Publisher
National Academy of Sciences
Citation
Winkler, Liu, Phong, Hinrichs, Ataii, Williams, Hadler-Olsen, Samson, Gartner, Fisher, Werb. Bisphenol A replacement chemicals, BPF and BPS, induce protumorigenic changes in human mammary gland organoid morphology and proteome. Proceedings of the National Academy of Sciences of the United States of America. 2022;119(11):1-10
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