Reversion of breast epithelial polarity alterations caused by obesity
Abstract Molecular links between breast cancer risk factors and pro-oncogenic tissue alterations are poorly understood. The goal of this study was to characterize the impact of overweight and obesity on tissue markers of risk, using normal breast biopsies, a mouse model of diet-induced obesity, and...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-023-00539-w |
| _version_ | 1797428998778650624 |
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| author | Julia Holmes Mohamed Gaber Mónica Z. Jenks Adam Wilson Tucker Loy Cassandra Lepetit Mara Z. Vitolins Brittney-Shea Herbert Katherine L. Cook Pierre-Alexandre Vidi |
| author_facet | Julia Holmes Mohamed Gaber Mónica Z. Jenks Adam Wilson Tucker Loy Cassandra Lepetit Mara Z. Vitolins Brittney-Shea Herbert Katherine L. Cook Pierre-Alexandre Vidi |
| author_sort | Julia Holmes |
| collection | DOAJ |
| description | Abstract Molecular links between breast cancer risk factors and pro-oncogenic tissue alterations are poorly understood. The goal of this study was to characterize the impact of overweight and obesity on tissue markers of risk, using normal breast biopsies, a mouse model of diet-induced obesity, and cultured breast acini. Proliferation and alteration of epithelial polarity, both necessary for tumor initiation, were quantified by immunostaining. High BMI (>30) and elevated leptin were associated with compromised epithelial polarity whereas overweight was associated with a modest increase in proliferation in human and mice mammary glands. Human serum with unfavorable adipokine levels altered epithelial polarization of cultured acini, recapitulating the effect of leptin. Weight loss in mice led to metabolic improvements and restored epithelial polarity. In acini cultures, alteration of epithelial polarity was prevented by antioxidants and could be reverted by normalizing culture conditions. This study shows that obesity and/or dietary factors modulate tissue markers of risk. It provides a framework to set target values for metabolic improvements and to assess the efficacy of interventional studies aimed at reducing breast cancer risk. |
| first_indexed | 2024-03-09T09:06:51Z |
| format | Article |
| id | doaj.art-309906a85b2744b2b45205e1539f6f80 |
| institution | Directory Open Access Journal |
| issn | 2374-4677 |
| language | English |
| last_indexed | 2024-03-09T09:06:51Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj.art-309906a85b2744b2b45205e1539f6f802023-12-02T10:08:55ZengNature Portfolionpj Breast Cancer2374-46772023-05-019111210.1038/s41523-023-00539-wReversion of breast epithelial polarity alterations caused by obesityJulia Holmes0Mohamed Gaber1Mónica Z. Jenks2Adam Wilson3Tucker Loy4Cassandra Lepetit5Mara Z. Vitolins6Brittney-Shea Herbert7Katherine L. Cook8Pierre-Alexandre Vidi9Department of Cancer Biology, Wake Forest University School of MedicineDepartment of Cancer Biology, Wake Forest University School of MedicineDepartment of Cancer Biology, Wake Forest University School of MedicineDepartment of Surgery, Wake Forest University School of MedicineDepartment of Cancer Biology, Wake Forest University School of MedicineInstitut de Cancérologie de l’OuestDepartment of Epidemiology and Prevention, Wake Forest University School of MedicineDepartment of Medical & Molecular Genetics, IU School of MedicineDepartment of Surgery, Wake Forest University School of MedicineDepartment of Cancer Biology, Wake Forest University School of MedicineAbstract Molecular links between breast cancer risk factors and pro-oncogenic tissue alterations are poorly understood. The goal of this study was to characterize the impact of overweight and obesity on tissue markers of risk, using normal breast biopsies, a mouse model of diet-induced obesity, and cultured breast acini. Proliferation and alteration of epithelial polarity, both necessary for tumor initiation, were quantified by immunostaining. High BMI (>30) and elevated leptin were associated with compromised epithelial polarity whereas overweight was associated with a modest increase in proliferation in human and mice mammary glands. Human serum with unfavorable adipokine levels altered epithelial polarization of cultured acini, recapitulating the effect of leptin. Weight loss in mice led to metabolic improvements and restored epithelial polarity. In acini cultures, alteration of epithelial polarity was prevented by antioxidants and could be reverted by normalizing culture conditions. This study shows that obesity and/or dietary factors modulate tissue markers of risk. It provides a framework to set target values for metabolic improvements and to assess the efficacy of interventional studies aimed at reducing breast cancer risk.https://doi.org/10.1038/s41523-023-00539-w |
| spellingShingle | Julia Holmes Mohamed Gaber Mónica Z. Jenks Adam Wilson Tucker Loy Cassandra Lepetit Mara Z. Vitolins Brittney-Shea Herbert Katherine L. Cook Pierre-Alexandre Vidi Reversion of breast epithelial polarity alterations caused by obesity npj Breast Cancer |
| title | Reversion of breast epithelial polarity alterations caused by obesity |
| title_full | Reversion of breast epithelial polarity alterations caused by obesity |
| title_fullStr | Reversion of breast epithelial polarity alterations caused by obesity |
| title_full_unstemmed | Reversion of breast epithelial polarity alterations caused by obesity |
| title_short | Reversion of breast epithelial polarity alterations caused by obesity |
| title_sort | reversion of breast epithelial polarity alterations caused by obesity |
| url | https://doi.org/10.1038/s41523-023-00539-w |
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