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Vitamin D3 regulates estrogen’s action and affects mammary epithelial organization in 3D cultures

Nafis Hasan, Carlos Sonnenschein, Ana M. Soto
doi: https://doi.org/10.1101/439307
Nafis Hasan
1Cell, Molecular & Developmental Biology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA.
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Carlos Sonnenschein
1Cell, Molecular & Developmental Biology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA.
2Department of Immunology, Tufts University School of Medicine, Boston, MA.
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Ana M. Soto
1Cell, Molecular & Developmental Biology Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA.
2Department of Immunology, Tufts University School of Medicine, Boston, MA.
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Abstract

Vitamin D3 (vitD3) and its active metabolite, calcitriol (1,25-(OH)2D3), affect multiple tissue types by interacting with the vitamin D receptor (VDR). Although vitD3 deficiency has been correlated with increased incidence of breast cancer and less favorable outcomes across ethnic groups and latitudes, randomized human clinical trials have yet to provide conclusive evidence on the efficacy of vitD3 in treating and/or preventing breast cancer. When considering that carcinogenesis is “development gone awry”, it becomes imperative to understand the role of vitD3 during breast development. Mammary gland development in VDR KO mice is altered by increased ductal elongation and lateral branching during puberty, precocious and increased alveologenesis at pregnancy and delayed post-lactational involution. These developmental processes are largely influenced by mammotropic hormones, i.e., ductal elongation by estrogen, branching by progesterone and alveologenesis by prolactin. However, research on vitD3’s effects on mammary gland morphogenesis focused on cell proliferation and apoptosis in 2D culture models and utilized supra-physiological doses of vitD3, conditions that spare the microenvironment in which morphogenesis takes place. Here, using two 3D culture models, we investigated the role of vitD3 in mammary epithelial morphogenesis. We found that vitD3 interferes with estrogen’s actions on T47D human breast cancer cells in 3D differently at different doses, and recapitulates what is observed in vivo. Also, vitD3 can act autonomously and affect the organization of MCF10A cells in 3D collagen matrix by influencing collagen fiber organization. Thus, we uncovered how vitD3 modulates mammary tissue organization independent of its already known effects on cell proliferation.

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  • Disclosures – The authors declare no competing financial interests.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 10, 2018.
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Vitamin D3 regulates estrogen’s action and affects mammary epithelial organization in 3D cultures
Nafis Hasan, Carlos Sonnenschein, Ana M. Soto
bioRxiv 439307; doi: https://doi.org/10.1101/439307
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Vitamin D3 regulates estrogen’s action and affects mammary epithelial organization in 3D cultures
Nafis Hasan, Carlos Sonnenschein, Ana M. Soto
bioRxiv 439307; doi: https://doi.org/10.1101/439307

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