Document Detail


The cytoplasmic domain of MUC1 induces hyperplasia in the mammary gland and correlates with nuclear accumulation of β-catenin.
MedLine Citation:
PMID:  21533058     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
MUC1 is an oncoprotein that is overexpressed in up to 90% of breast carcinomas. A previous in vitro study by our group demonstrated that the cytoplasmic domain of MUC1 (MUC1-CD), the minimal functional unit of MUC1, contributes to the malignant phenotype in cells by binding directly to β-catenin and protecting β-catenin from GSK3β-induced degradation. To understand the in vivo role of MUC1-CD in breast development, we generated a MUC1-CD transgenic mouse model under the control of the MMTV promoter in a C57BL/6J background, which is more resistant to breast tumor. We show that the expression of MUC1-CD in luminal epithelial cells of the mammary gland induced a hyperplasia phenotype characterized by the development of hyper-branching and extensive lobuloalveoli in transgenic mice. In addition to this hyperplasia, there was a marked increase in cellular proliferation in the mouse mammary gland. We further show that MUC1-CD induces nuclear localization of β-catenin, which is associated with a significant increase of β-catenin activity, as shown by the elevated expression of cyclin D1 and c-Myc in MMTV-MUC1-CD mice. Consistent with this finding, we observed that overexpression of MUC1-C is associated with β-catenin nuclear localization in tumor tissues and increased expression of Cyclin D1 and c-Myc in breast carcinoma specimens. Collectively, our data indicate a critical role for MUC1-CD in the development of mammary gland preneoplasia and tumorigenesis, suggesting MUC1-CD as a potential target for the diagnosis and chemoprevention of human breast cancer.
Authors:
Yuan Li; Haiying Yi; Yixin Yao; Xiaodong Liao; Yiqun Xie; Jie Yang; Zheng Yan; Long Wang; Shunyuan Lu; Ying Kuang; Mingmin Gu; Jian Fei; Zhugang Wang; Lei Huang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-20
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-05-02     Completed Date:  2011-08-30     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e19102     Citation Subset:  IM    
Affiliation:
Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Breast Neoplasms / metabolism,  pathology
Cell Nucleus / metabolism*
Cell Proliferation
Cytoplasm / metabolism*
Female
Hyperplasia / pathology*
Mammary Glands, Animal / metabolism,  pathology*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mucin-1 / chemistry,  metabolism,  physiology*
Chemical
Reg. No./Substance:
0/Mucin-1
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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