Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/144610
Title: Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism
Authors: Lim, Chew Leng
Or, Yu Zuan
Ong, Zoe
Chung, Hwa Hwa
Hayashi, Hirohito
Shrestha, Smeeta
Chiba, Shunsuke
Lin, Feng
Lin, Valerie Chun Ling
Keywords: Science::Medicine
Issue Date: 2020
Source: 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
Journal: eLife
Abstract: 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.
URI: https://hdl.handle.net/10356/144610
ISSN: 2050-084X
DOI: 10.7554/eLife.57274
Rights: © 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.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:IGS Journal Articles

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