Mammary gland development and EDC-driven cancer susceptibility in mesenchymal ERα-knockout mice

in Endocrine-Related Cancer
Authors:
Clarissa Wormsbaecher Department of Molecular Genetics, The Ohio State University, Columbus, Ohio, USA
The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA

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Brittney M Cumbia The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA

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Emma G Amurgis The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA

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Jillian M Poska Department of Molecular Genetics, The Ohio State University, Columbus, Ohio, USA
The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA

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Madeline R Price Department of Molecular Genetics, The Ohio State University, Columbus, Ohio, USA
The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA

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Xiaokui M Mo Department of Biomedical Informatics, Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA

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Sue E Knoblaugh Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA

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Takeshi Kurita The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA
Department of Cancer Biology and Genetics, The Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA

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Craig Joseph Burd Department of Molecular Genetics, The Ohio State University, Columbus, Ohio, USA
The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA

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Correspondence should be addressed to C J Burd: craig.burd@osumc.edu
DOI:
https://doi.org/10.1530/ERC-23-0062
Volume/Issue:
Volume 30: Issue 12
Article Type:
Research Article
Article ID:
e230062
Online Publication Date:
14 Nov 2023
Copyright:
© the author(s) 2023
Restricted access
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Development of the mammary gland requires both proper hormone signaling and cross talk between the stroma and epithelium. While estrogen receptor (ERα) expression in the epithelium is essential for normal gland development, the role of this receptor in the stroma is less clear. Moreover, several lines of evidence suggest that mouse phenotypes of in utero exposure to endocrine disruption act through mesenchymal ERα in the developing fetus. We utilized a Twist2-cre mouse line to knock out mesenchymal ERα. Herein, we assessed mammary gland development in the context of mesenchymal ERα deletion. We also tested the effect of in utero bisphenol A (BPA) exposure to alter the tumor susceptibility in the mouse mammary tumor virus-neu (MMTV-neu) breast cancer mouse model. Mesenchymal ERα deletion resulted in altered reproductive tract development and atypical cytology associated with estrous cycling. The mammary gland demonstrated mature epithelial extension unlike complete ERα-knockout mice, but ductal extension was delayed and reduced compared to ERα-competent mice. Using the MMTV-Neu cancer susceptibility model, ERα-intact mice exposed to BPA had reduced tumor-free survival and overall survival compared to BPA-exposed mice having mesenchymal ERα deletion. This difference is specific for BPA exposure as vehicle-treated animals had no difference in tumor development between mice expressing and not expressing mesenchymal ERα. These data demonstrate that mesenchymal ERα expression is not required for ductal extension, nor does it influence cancer risk in this mouse model but does influence the cancer incidence associated with in utero BPA exposure.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2023
Article ID:
e230062
Received Date:
08 Mar 2023
Accepted Date:
11 Oct 2023
Print Publication Date:
01 Dec 2023
Online Publication Date:
14 Nov 2023
Keywords:
endocrine disruptors; mammary gland; estrogen receptor; MMTV-Neu

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