Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism
There is strong evidence that the pro-inflammatory microenvironment during post-partum mammary involution promotes parity-associated breast cancer. Estrogen exposure during mammary involution drives tumor growth through neutrophils' activity. However, how estrogen and neutrophils influence mamm...
| Main Authors: | , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2020
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| Online Access: | https://hdl.handle.net/10356/144610 |
| _version_ | 1811677443029729280 |
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| author | Lim, Chew Leng Or, Yu Zuan Ong, Zoe Chung, Hwa Hwa Hayashi, Hirohito Shrestha, Smeeta Chiba, Shunsuke Lin, Feng Lin, Valerie Chun Ling |
| author2 | School of Computer Science and Engineering |
| author_facet | School of Computer Science and Engineering Lim, Chew Leng Or, Yu Zuan Ong, Zoe Chung, Hwa Hwa Hayashi, Hirohito Shrestha, Smeeta Chiba, Shunsuke Lin, Feng Lin, Valerie Chun Ling |
| author_sort | Lim, Chew Leng |
| collection | NTU |
| description | There is strong evidence that the pro-inflammatory microenvironment during post-partum mammary involution promotes parity-associated breast cancer. Estrogen exposure during mammary involution drives tumor growth through neutrophils' activity. However, how estrogen and neutrophils influence mammary involution are unknown. Combined analysis of transcriptomic, protein, and immunohistochemical data in BALB/c mice showed that estrogen promotes involution by exacerbating inflammation, cell death and adipocytes repopulation. Remarkably, 88% of estrogen-regulated genes in mammary tissue were mediated through neutrophils, which were recruited through estrogen-induced CXCR2 signalling in an autocrine fashion. While neutrophils mediate estrogen-induced inflammation and adipocytes repopulation, estrogen-induced mammary cell death was via lysosome-mediated programmed cell death through upregulation of cathepsin B, Tnf and Bid in a neutrophil-independent manner. Notably, these multifaceted effects of estrogen are mostly mediated by ERα and unique to the phase of mammary involution. These findings are important for the development of intervention strategies for parity-associated breast cancer. |
| first_indexed | 2024-10-01T02:37:27Z |
| format | Journal Article |
| id | ntu-10356/144610 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:37:27Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1446102023-03-05T16:28:12Z Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism Lim, Chew Leng Or, Yu Zuan Ong, Zoe Chung, Hwa Hwa Hayashi, Hirohito Shrestha, Smeeta Chiba, Shunsuke Lin, Feng Lin, Valerie Chun Ling School of Computer Science and Engineering School of Biological Sciences School of Physical and Mathematical Sciences Interdisciplinary Graduate School (IGS) Science::Medicine Human Estrogen There is strong evidence that the pro-inflammatory microenvironment during post-partum mammary involution promotes parity-associated breast cancer. Estrogen exposure during mammary involution drives tumor growth through neutrophils' activity. However, how estrogen and neutrophils influence mammary involution are unknown. Combined analysis of transcriptomic, protein, and immunohistochemical data in BALB/c mice showed that estrogen promotes involution by exacerbating inflammation, cell death and adipocytes repopulation. Remarkably, 88% of estrogen-regulated genes in mammary tissue were mediated through neutrophils, which were recruited through estrogen-induced CXCR2 signalling in an autocrine fashion. While neutrophils mediate estrogen-induced inflammation and adipocytes repopulation, estrogen-induced mammary cell death was via lysosome-mediated programmed cell death through upregulation of cathepsin B, Tnf and Bid in a neutrophil-independent manner. Notably, these multifaceted effects of estrogen are mostly mediated by ERα and unique to the phase of mammary involution. These findings are important for the development of intervention strategies for parity-associated breast cancer. Ministry of Education (MOE) Published version This research is funded the Ministry of Education of Singapore. Academic Research Fund Tier I, MOE2017-T1-002-081. We thank Drs. Natasa Bajalovic, Amanda Woo and Mr. Lee Shi Hao for their technical assistance. 2020-11-16T02:29:23Z 2020-11-16T02:29:23Z 2020 Journal Article Lim, C. L., Or, Y. Z., Ong, Z., Chung, H. H., Hayashi, H., Shrestha, S., . . . Lin, V. C. L. (2020). Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism. ELife, 9, e57274. doi:10.7554/elife.57274 2050-084X https://hdl.handle.net/10356/144610 10.7554/eLife.57274 32706336 9 en eLife © 2020 Lim et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. application/pdf |
| spellingShingle | Science::Medicine Human Estrogen Lim, Chew Leng Or, Yu Zuan Ong, Zoe Chung, Hwa Hwa Hayashi, Hirohito Shrestha, Smeeta Chiba, Shunsuke Lin, Feng Lin, Valerie Chun Ling Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism |
| title | Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism |
| title_full | Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism |
| title_fullStr | Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism |
| title_full_unstemmed | Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism |
| title_short | Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism |
| title_sort | estrogen exacerbates mammary involution through neutrophil dependent and independent mechanism |
| topic | Science::Medicine Human Estrogen |
| url | https://hdl.handle.net/10356/144610 |
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