MUC1 induces M2 type macrophage influx during postpartum mammary gland involution and triggers breast cancer.
MUC1 induces M2 type macrophage influx during postpartum mammary gland involution and triggers breast cancer.
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MUC1在产后乳腺退化过程中诱导M2型巨噬细胞流入并引发乳腺癌
DOI：
10.18632/oncotarget.23316
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发表时间：
2018-01-09
期刊：
影响因子：
--
通讯作者：
Huang L
中科院分区：
文献类型：
--
作者：
Li Y;Pang Z;Dong X;Liao X;Deng H;Liao C;Liao Y;Chen G;Huang L
产后乳腺复旧（PMI）的微环境与乳腺癌风险增加和患者预后不良有关。然而，调控微环境的机制在很大程度上仍然未知。MUC1在大多数乳腺癌中异常过表达，在PMI中有生理性表达。通过MUC1细胞质结构域（MUC1- cd）转基因小鼠，我们发现MUC1- cd在乳腺上皮细胞中的过表达增加了PMI中M2型巨噬细胞的浸润。通过持续激活p50， MUC1上调M2巨噬细胞化学引诱剂和抗凋亡蛋白Bcl-xL。由于肿瘤促进微环境和细胞凋亡的减少，MUC1-CD延缓了PMI过程，导致多产小鼠乳腺的非典型表型。通过对乳腺癌数据库的分析，MUC1和p50在Luminal A和Luminal B亚型中的表达呈正相关，进一步支持了这一发现。综上所述，我们的研究表明MUC1-CD在调节PMI微环境和促进产后乳腺致瘤性中发挥重要作用，为产后乳腺癌的预防和治疗提供了新的策略。
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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DOI：
10.1186/bcr3633
发表时间：
2014-03-28
期刊：
Breast cancer research : BCR
影响因子：
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作者：
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发表时间：
2016-10
期刊：
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Fingleton B
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通讯作者：
Kufe, Donald W.
影响因子：
2.5
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Fornetti, Jaime;Martinson, Holly A.;Betts, Courtney B.;Lyons, Traci R.;Jindal, Sonali;Guo, Qiuchen;Coussens, Lisa M.;Borges, Virginia F.;Schedin, Pepper
通讯作者：
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