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Loss of Core 1-derived O-Glycans Decreases Breast Cancer Development in Mice
Authors:Kai Song  Brett H. Herzog  Jianxin Fu  Minjia Sheng  Kirk Bergstrom  J. Michael McDaniel  Yuji Kondo  Samuel McGee  Xiaofeng Cai  Ping Li  Hong Chen  Lijun Xia
Abstract:Mucin-type core 1-derived O-glycans, one of the major types of O-glycans, are highly expressed in mammary gland epithelium. Abnormal O-glycans such as Tn antigen are found in over 90% of breast cancers; however, the in vivo role of these aberrant O-glycans in the etiology of breast cancer is unclear. We generated mice with mammary epithelial specific deletion of core 1-derived O-glycans. By crossing with two spontaneous mouse breast cancer models, we determined that loss of core 1-derived O-glycans delays the onset and progression of breast cancer development. Deficiency of core 1 O-glycosylation impaired the localization of Muc1, a major O-glycoprotein, on the apical surfaces of mammary epithelium. Signaling mediated by Muc1, which is critical for breast cancer development, was also defective in the absence of core 1 O-glycans. This study reveals an unexpected role of core 1-derived O-glycans in breast cancer development in mice.
Keywords:breast cancer   cell proliferation   glycosylation   mouse   mucin 1   cell surface associated (MUC1)   tumor microenvironment
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