Desensitization of human breast progenitors by a transient exposure to pregnancy levels of estrogen
Abstract Full term pregnancy at an early age is the only factor known to consistently protect against breast cancer. Because hormone receptor positive progenitors in the human breast relay endocrine signaling, we here sought to determine whether an experimental mimicry of the third trimester surge o...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-96785-8 |
| _version_ | 1818423254289743872 |
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| author | Lone Rønnov-Jessen Jiyoung Kim Nadine Goldhammer Marie Christine Klitgaard Martynas Smicius Marc Baker Bechmann René Villadsen Ole William Petersen |
| author_facet | Lone Rønnov-Jessen Jiyoung Kim Nadine Goldhammer Marie Christine Klitgaard Martynas Smicius Marc Baker Bechmann René Villadsen Ole William Petersen |
| author_sort | Lone Rønnov-Jessen |
| collection | DOAJ |
| description | Abstract Full term pregnancy at an early age is the only factor known to consistently protect against breast cancer. Because hormone receptor positive progenitors in the human breast relay endocrine signaling, we here sought to determine whether an experimental mimicry of the third trimester surge of hormones would change their susceptibility to growth stimulation. Hormone receptor positive, reduction mammoplasty-derived human breast epithelial progenitors were exposed to a short-term, pregnancy-level of estradiol, and their subsequent response to estradiol stimulation was analyzed. Exposure to pregnancy-level of estradiol results in subsequent lower sensitivity to estrogen-induced proliferation. Expression array and immunoblotting reveal upregulation of S100A7 and down-regulation of p27, both associated with parity and epithelial differentiation. Notably, we find that the epithelial differentiation is accompanied by upregulation of E-cadherin and down-regulation of vimentin as well as by diminished migration and more mature luminal epithelial differentiation in a mouse transplantation model. Our findings are in support of a de-sensitization mechanism for pregnancy-induced prevention against breast cancer. |
| first_indexed | 2024-12-14T13:39:13Z |
| format | Article |
| id | doaj.art-9d1066b65c1f4879aa2a803d4e53a46b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T13:39:13Z |
| publishDate | 2021-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-9d1066b65c1f4879aa2a803d4e53a46b2022-12-21T22:59:30ZengNature PortfolioScientific Reports2045-23222021-08-011111710.1038/s41598-021-96785-8Desensitization of human breast progenitors by a transient exposure to pregnancy levels of estrogenLone Rønnov-Jessen0Jiyoung Kim1Nadine Goldhammer2Marie Christine Klitgaard3Martynas Smicius4Marc Baker Bechmann5René Villadsen6Ole William Petersen7Section for Cell Biology and Physiology, Department of Biology, University of CopenhagenDepartment of Cellular and Molecular Medicine, University of CopenhagenDepartment of Cellular and Molecular Medicine, University of CopenhagenSection for Cell Biology and Physiology, Department of Biology, University of CopenhagenSection for Cell Biology and Physiology, Department of Biology, University of CopenhagenSection for Cell Biology and Physiology, Department of Biology, University of CopenhagenDepartment of Cellular and Molecular Medicine, University of CopenhagenDepartment of Cellular and Molecular Medicine, University of CopenhagenAbstract Full term pregnancy at an early age is the only factor known to consistently protect against breast cancer. Because hormone receptor positive progenitors in the human breast relay endocrine signaling, we here sought to determine whether an experimental mimicry of the third trimester surge of hormones would change their susceptibility to growth stimulation. Hormone receptor positive, reduction mammoplasty-derived human breast epithelial progenitors were exposed to a short-term, pregnancy-level of estradiol, and their subsequent response to estradiol stimulation was analyzed. Exposure to pregnancy-level of estradiol results in subsequent lower sensitivity to estrogen-induced proliferation. Expression array and immunoblotting reveal upregulation of S100A7 and down-regulation of p27, both associated with parity and epithelial differentiation. Notably, we find that the epithelial differentiation is accompanied by upregulation of E-cadherin and down-regulation of vimentin as well as by diminished migration and more mature luminal epithelial differentiation in a mouse transplantation model. Our findings are in support of a de-sensitization mechanism for pregnancy-induced prevention against breast cancer.https://doi.org/10.1038/s41598-021-96785-8 |
| spellingShingle | Lone Rønnov-Jessen Jiyoung Kim Nadine Goldhammer Marie Christine Klitgaard Martynas Smicius Marc Baker Bechmann René Villadsen Ole William Petersen Desensitization of human breast progenitors by a transient exposure to pregnancy levels of estrogen Scientific Reports |
| title | Desensitization of human breast progenitors by a transient exposure to pregnancy levels of estrogen |
| title_full | Desensitization of human breast progenitors by a transient exposure to pregnancy levels of estrogen |
| title_fullStr | Desensitization of human breast progenitors by a transient exposure to pregnancy levels of estrogen |
| title_full_unstemmed | Desensitization of human breast progenitors by a transient exposure to pregnancy levels of estrogen |
| title_short | Desensitization of human breast progenitors by a transient exposure to pregnancy levels of estrogen |
| title_sort | desensitization of human breast progenitors by a transient exposure to pregnancy levels of estrogen |
| url | https://doi.org/10.1038/s41598-021-96785-8 |
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