ArticleBreast cancer research : BCR2020
In utero estrogenic endocrine disruption alters the stroma to increase extracellular matrix density and mammary gland stiffness.
Article in Breast cancer research : BCR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Bisphenol A and breast cancer: Can mechanistic plausibility be reconciled with epidemiological inconsistency?iScience · 2026Review
- Rethinking the microenvironment's role in chemical-induced malignancy.Toxicological sciences : an official journal of the Society of Toxicology · 2026Review
- An in utero exposure to the synthetic estrogen diethylstilbestrol affects the fat pad composition in post-natal mammary glands.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Multifaceted mechanisms by which environmental endocrine-disrupting chemicals promote cancer progression: crosstalk among carcinogenesis, immunity, and metabolic reprogramming: narrative mini-review.Frontiers in molecular biosciences · 2026Review
- Bisphenol A (BPA) Modifies Cancer Signaling Pathways: A Neglected Global Health Threat.Journal of xenobiotics · 2025Review
- In utero exposure to estrogenic bisphenol analogues increases mammary tissue stiffness.Reproductive toxicology (Elmsford, N.Y.) · 2025Article
- Analysis of miRNAs in milk of four livestock species.BMC genomics · 2024Article
- Biological Basis of Breast Cancer-Related Disparities in Precision Oncology Era.International journal of molecular sciences · 2024Review
- Breast Cancer Exposomics.Life (Basel, Switzerland) · 2024Review
- Onco-Breastomics: An Eco-Evo-Devo Holistic Approach.International journal of molecular sciences · 2024Review
- Mammary gland development and EDC-driven cancer susceptibility in mesenchymal ERα-knockout mice.Endocrine-related cancer · 2023Article
- Chemical Effects on Breast Development, Function, and Cancer Risk: Existing Knowledge and New Opportunities.Current environmental health reports · 2022Review
- Sex-specific extracellular matrix remodeling during early adipogenic differentiation by gestational bisphenol A exposure.Chemosphere · 2022Article
- Potential Pro-Tumorigenic Effect of Bisphenol A in Breast Cancer via Altering the Tumor Microenvironment.Cancers · 2022Review
- The Role of microRNAs in the Mammary Gland Development, Health, and Function of Cattle, Goats, and Sheep.Non-coding RNA · 2021Review
- Are the Effects of DES Over? A Tragic Lesson from the Past.International journal of environmental research and public health · 2021Review
- Endocrine-Disrupting Chemicals' (EDCs) Effects on Tumour Microenvironment and Cancer Progression: Emerging Contribution of RACK1.International journal of molecular sciences · 2020Review
- Exposure to Endocrine Disrupting Chemicals and Risk of Breast Cancer.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
backgroundIn utero endocrine disruption is linked to increased risk of breast cancer later in life. Despite numerous studies establishing this linkage, the long-term molecular changes that predispose mammary cells to carcinogenic transformation are unknown. Herein, we investigated how endocrine disrupting compounds (EDCs) drive changes within the stroma that can contribute to breast cancer susceptibility.
methodsWe utilized bisphenol A (BPA) as a model of estrogenic endocrine disruption to analyze the long-term consequences in the stroma. Deregulated genes were identified by RNA-seq transcriptional profiling of adult primary fibroblasts, isolated from female mice exposed to in utero BPA. Collagen staining, collagen imaging techniques, and permeability assays were used to characterize changes to the extracellular matrix. Finally, gland stiffness tests were performed on exposed and control mammary glands.
resultsWe identified significant transcriptional deregulation of adult fibroblasts exposed to in utero BPA. Deregulated genes were associated with cancer pathways and specifically extracellular matrix composition. Multiple collagen genes were more highly expressed in the BPA-exposed fibroblasts resulting in increased collagen deposition in the adult mammary gland. This transcriptional reprogramming of BPA-exposed fibroblasts generates a less permeable extracellular matrix and a stiffer mammary gland. These phenotypes were only observed in adult 12-week-old, but not 4-week-old, mice. Additionally, diethylstilbestrol, known to increase breast cancer risk in humans, also increases gland stiffness similar to BPA, while bisphenol S does not.
conclusionsAs breast stiffness, extracellular matrix density, and collagen deposition have been directly linked to breast cancer risk, these data mechanistically connect EDC exposures to molecular alterations associated with increased disease susceptibility. These alterations develop over time and thus contribute to cancer risk in adulthood.
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