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Please use this identifier to cite or link to this item: http://bura.brunel.ac.uk/handle/2438/7009

Title: Disruption of 3D MCF-12A breast cell cultures by estrogens - An in vitro model for ER-mediated changes indicative of hormonal carcinogenesis
Authors: Marchese, S
Silva, E
Publication Date: 2012
Publisher: Public Library of Science
Citation: PLoS ONE, 7(10): e45767, Oct 2012
Abstract: Introduction: Estrogens regulate the proliferation of normal and neoplastic breast epithelium. Although the intracellular mechanisms of estrogens in the breast are largely understood, little is known about how they induce changes in the structure of the mammary epithelium, which are characteristic of breast cancer. In vitro three dimensional (3D) cultures of immortalised breast epithelial cells recapitulate features of the breast epithelium in vivo, including formation of growth arrested acini with hollow lumen and basement membrane. This model can also reproduce features of malignant transformation and breast cancer, such as increased cellular proliferation and filling of the lumen. However, a system where a connection between estrogen receptor (ER) activation and disruption of acini formation can be studied to elucidate the role of estrogens is still missing. Methods/Principal Findings: We describe an in vitro 3D model for breast glandular structure development, using breast epithelial MCF-12A cells cultured in a reconstituted basement membrane matrix. These cells are estrogen receptor (ER)α, ERβ and G-protein coupled estrogen receptor 1 (GPER) competent, allowing the investigation of the effects of estrogens on mammary gland formation and disruption. Under normal conditions, MCF-12A cells formed organised acini, with deposition of basement membrane and hollow lumen. However, treatment with 17β-estradiol, and the exogenous estrogens bisphenol A and propylparaben resulted in deformed acini and filling of the acinar lumen. When these chemicals were combined with ER and GPER inhibitors (ICI 182,780 and G-15, respectively), the deformed acini recovered normal features, such as a spheroid shape, proliferative arrest and luminal clearing, suggesting a role for the ER and GPER in the estrogenic disruption of acinar formation. Conclusion: This new model offers the opportunity to better understand the role of the ER and GPER in the morphogenesis of breast glandular structure as well as the events implicated in breast cancer initiation and progression.
Description: Copyright @ 2012 The Authors. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and 85 reproduction in any medium, provided the original author and source are credited. The article was made available through the Brunel University Open Access Publishing Fund.
Sponsorship: This study was partly funded by a School of Pharmacy Studentship.
URI: http://www.plosone.org/article/info%3Adoi/10.1371/journal.pone.0045767
http://bura.brunel.ac.uk/handle/2438/7009
DOI: http://dx.doi.org/10.1371/journal.pone.0045767
ISSN: 1932-6203
Appears in Collections:Environment
Brunel OA Publishing Fund
Institute for the Environment

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