MUC1 induces M2 type macrophage influx during postpartum mammary gland involution and triggers breast cancer
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Yuan Li1,2,*, Zhi Pang1,*, Xinran Dong3,*, Xiaodong Liao1,4,*, Huayun Deng1,4, Chunhua Liao1, Yahui Liao1, Guoqiang Chen1 and Lei Huang1,4
1Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
2Department of Endocrinology, Huadong Hospital Affiliated to Fudan University, Shanghai, P.R. China
3Key Laboratory of Birth Defects, Children’s Hospital of Fudan University, Shanghai, P.R. China
4Department of Histoembryology, Genetics and Developmental Biology, Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
*These authors contributed equally to this work
Lei Huang, email: firstname.lastname@example.org
Keywords: MUC1-CD; involution; M2 macrophages; p50; breast cancer
Received: August 24, 2017 Accepted: November 19, 2017 Published: December 15, 2017
The microenvironment of postpartum mammary gland involution (PMI) has been linked to the increased risk of breast cancer and poor outcome of patients. Nevertheless the mechanism underlying regulates the microenvironment remains largely unknown. MUC1, which is abnormally overexpressed in most breast cancer, is physiologically expressed in PMI. Using MUC1 cytoplasm domain (MUC1-CD) transgenic mice, we reveal that the overexpression of MUC1-CD in mammary epithelial cells increases M2 type macrophage infiltration in PMI. By sustain activating p50, MUC1 upregulates M2 macrophage chemo-attractants and the anti-apoptotic protein Bcl-xL. Because of the tumor promotional microenvironments and reduced apoptosis, MUC1-CD delays PMI process and results in atypical phenotype in multiparous mice mammary. This finding is further supported by the positive association between the expression of MUC1 and p50 in Luminal A and Luminal B subtypes through analyzing breast cancer databases. Taken together, our study demonstrates that MUC1-CD plays an important role in regulating microenvironment of PMI and promoting postpartum mammary tumorigenicity, providing novel prevention and treatment strategies against postpartum breast cancer.
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