Characterizing neutrophil response to estrogen during mammary involution
Date of Issue2017-03-29
School of Biological Sciences
Women, especially those who experienced first full-term pregnancy at late age, face increased risk of pregnancy-associated breast cancer (PABC) in 10 years following childbirth. Mammary involution has been implicated as a key risk factor due to its inflammatory nature. Estrogen exposure is also another risk factor for breast cancer, but its specific effect during mammary involution has yet to be elucidated. Here, we showed that estrogen exposure during mammary involution locally amplifies the inflammatory response by enhancing neutrophil chemotaxis in a CXCR2-dependent manner, and differentiated estrogen-regulated functions of cell growth and death from neutrophil-regulated functions of neutrophil recruitment and adipogenesis. These findings highlight a novel mechanism of estrogenic action on neutrophils during mammary involution. This could be useful for development of novel therapeutics for PABC that are specific to the context of estrogen exposure during mammary involution.