Loss of Core 1-derived O-Glycans Decreases Breast Cancer Development in Mice.

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.

• 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
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 33 Pg. 20159-66 (Aug 14 2015) ISSN: 1083-351X [Electronic] United States
• PMID: 26124270 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Polysaccharides

Topics

• Animals
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Proliferation
• Disease Models, Animal
• Female
• Genes, erbB-2
• Glycosylation
• Mice
• Polysaccharides (metabolism)