| Autor: |
Murrow, Lyndsay M, Weber, Robert J, Caruso, Joseph A, McGinnis, Christopher S, Phong, Kiet, Gascard, Philippe, Borowsky, Alexander D, Desai, Tejal A, Thomson, Matthew, Tlsty, Thea, Gartner, Zev J |
| Rok vydání: |
2018 |
| Předmět: |
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| Popis: |
The human breast undergoes lifelong remodeling in response to estrogen and progesterone, but hormone exposure also increases breast cancer risk. Here, we use single-cell analysis to identify distinct mechanisms through which breast composition and cell state affect hormone signaling. We show that prior pregnancy reduces the transcriptional response of hormone-responsive (HR+) epithelial cells, whereas high body mass index (BMI) reduces overall HR+ cell proportions. These distinct changes both impact neighboring cells by effectively reducing the magnitude of paracrine signals originating from HR+ cells. Because pregnancy and high BMI are known to protect against hormone-dependent breast cancer in premenopausal women, our findings directly link breast cancer risk with person-to-person heterogeneity in hormone responsiveness. More broadly, our findings illustrate how cell proportions and cell state can collectively impact cell communities through the action of cell-to-cell signaling networks. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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