Document Detail


HuR is necessary for mammary epithelial cell proliferation and polarity at least in part via ΔNp63.
MedLine Citation:
PMID:  23028944     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
HuR, a RNA binding protein, is known to function as a tumor maintenance gene in breast cancer and associated with tumor growth and poor prognosis. However, the cellular function of this protein remains largely unknown in normal mammary epithelial cells. Here, we showed that in immortalized MCF10A mammary epithelial cells, HuR knockdown inhibits cell proliferation and enhances premature senescence. We also showed that in three-dimensional culture, MCF10A cells with HuR knockdown form abnormal acini with filled lumen and an aberrant expression pattern of the extracellular matrix protein laminin V. In addition, we showed that HuR knockdown increases ΔNp63, but decreases wild-type p53, expression in MCF10A cells. Moreover, we showed that ΔNp63 knockdown partially rescues the proliferative defect induced by HuR knockdown in MCF10A cells. Consistent with this, we identified two U-rich elements in the 3'-untranslated region of p63 mRNA, to which HuR specifically binds. Finally, we showed that HuR knockdown enhances ΔNp63 mRNA translation but has no effect on p63 mRNA turnover. Together, our data suggest that HuR maintains cell proliferation and polarity of mammary epithelial cells at least in part via ΔNp63.
Authors:
Wensheng Yan; Yanhong Zhang; Jin Zhang; Seong-Jun Cho; Xinbin Chen
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-09-18
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-02-25     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e45336     Citation Subset:  IM    
Affiliation:
Comparative Oncology Laboratory, University of California Davis, Davis, California, United States of America.
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MeSH Terms
Descriptor/Qualifier:
3' Untranslated Regions / genetics
Cell Line
Cell Polarity / physiology*
Cell Proliferation
Electrophoretic Mobility Shift Assay
Epithelial Cells / cytology*,  metabolism*
Hu Paraneoplastic Encephalomyelitis Antigens / genetics,  metabolism*
Humans
Mammary Glands, Human / cytology*
Membrane Proteins / genetics,  metabolism*
Microscopy, Confocal
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
R01 CA102188/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/3' Untranslated Regions; 0/CKAP4 protein, human; 0/Hu Paraneoplastic Encephalomyelitis Antigens; 0/Membrane Proteins
Comments/Corrections

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