Document Detail


Mammary epithelial cell polarity is regulated differentially by p73 isoforms via epithelial-to-mesenchymal transition.
MedLine Citation:
PMID:  22457351     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
p73 is expressed as TA and ΔN isoforms, both of which are implicated in tumor suppression and/or promotion. To address how p73 possesses these opposing functions, we developed three-dimensional culture of MCF10A cells, which undergo cell morphogenesis to form polarized spheroids with hollow lumen similar to normal mammary acini in vivo. Here, we showed that upon knockdown of p73, particularly TAp73 but not ΔNp73, MCF10A cells formed irregular and near-normal acini without hollow lumen in three-dimensional culture. We also found that upon knockdown of p73 or TAp73, but not ΔNp73, MCF10A cells underwent epithelial-to-mesenchymal transition (EMT) via down-regulation of E-cadherin coupled with up-regulation of β-catenin and laminin V. In addition, we found that Snail-1, Slug, and Twist, all of which are known to act as EMT inducers by repressing E-cadherin expression, were increased markedly upon knockdown of p73 and TAp73 but little if any by ΔNp73. Furthermore, we showed that knockdown of p73 or TAp73 in MCF10A cells led to a marked increase in cell proliferation and migration. Together, our data suggest that TAp73 is necessary for maintaining normal cell polarity by suppressing EMT.
Authors:
Yanhong Zhang; Wensheng Yan; Yong Sam Jung; Xinbin Chen
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-03-28
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-21     Completed Date:  2012-07-23     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17746-53     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cadherins / biosynthesis,  genetics
Cell Adhesion Molecules / biosynthesis,  genetics
Cell Line, Transformed
Cell Polarity / physiology*
Cell Proliferation
DNA-Binding Proteins / genetics,  metabolism*
Down-Regulation / physiology
Epithelial Cells / cytology,  metabolism*
Epithelial-Mesenchymal Transition / physiology*
Female
Gene Knockdown Techniques
Humans
Mammary Glands, Human / cytology,  metabolism*
Nuclear Proteins / biosynthesis,  genetics,  metabolism*
Spheroids, Cellular / cytology,  metabolism
Transcription Factors / biosynthesis,  genetics
Tumor Suppressor Proteins / genetics,  metabolism*
Twist Transcription Factor / biosynthesis,  genetics
Up-Regulation / physiology
beta Catenin / biosynthesis,  genetics
Grant Support
ID/Acronym/Agency:
CA081237/CA/NCI NIH HHS; R01 CA081237/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Cadherins; 0/Cell Adhesion Molecules; 0/DNA-Binding Proteins; 0/Nuclear Proteins; 0/TWIST1 protein, human; 0/Transcription Factors; 0/Tumor Suppressor Proteins; 0/Twist Transcription Factor; 0/beta Catenin; 0/kalinin; 0/snail family transcription factors; 0/tumor suppressor protein p73
Comments/Corrections

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


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