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Title: Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution
Authors: Chung, Hwa Hwa
Or, Yu Zuan
Shrestha, Smeeta
Loh, Jia Tong
Lim, Chew Leng
Ong, Zoe
Woo, Amanda Rui En
Su, I-hsin
Lin, Valerie Chun Ling
Keywords: Estrogen
Mammary Involution
Issue Date: 2017
Source: Chung, H. H., Or, Y. Z., Shrestha, S., Loh, J. T., Lim, C. L., Ong, Z., et al. (2017). Estrogen reprograms the activity of neutrophils to foster protumoral microenvironment during mammary involution. Scientific Reports, 7, 46485-.
Series/Report no.: Scientific Reports
Abstract: Epidemiological studies have indicated increased risk for breast cancer within 10 years of childbirth. Acute inflammation during mammary involution has been suggested to promote this parity-associated breast cancer. We report here that estrogen exacerbates mammary inflammation during involution. Microarray analysis shows that estrogen induces an extensive proinflammatory gene signature in the involuting mammary tissue. This is associated with estrogen-induced neutrophil infiltration. Furthermore, estrogen induces the expression of protumoral cytokines/chemokines, COX-2 and tissue-remodeling enzymes in isolated mammary neutrophils and systemic neutrophil depletion abolished estrogen-induced expression of these genes in mammary tissue. More interestingly, neutrophil depletion diminished estrogen-induced growth of ERα-negative mammary tumor 4T1 in Balb/c mice. These findings highlight a novel aspect of estrogen action that reprograms the activity of neutrophils to create a pro-tumoral microenvironment during mammary involution. This effect on the microenvironment would conceivably aggravate its known neoplastic effect on mammary epithelial cells.
ISSN: 2045-2322
DOI: 10.1038/srep46485
Rights: © 2017 The Author(s) (Nature Publishing Group). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
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