Document Detail

Tumor-induced upregulation of Twist, Snail, and Slug represses the activity of the human VE-cadherin promoter.
MedLine Citation:
PMID:  19046938     Owner:  NLM     Status:  MEDLINE    
Endothelial integrity is dependent on intracellular adherens junctions formed by complexes of vascular endothelial (VE)-cadherin and catenins. We have previously demonstrated that exposing endothelial cells (EC) to breast cancer cell-conditioned media (CM) for 24h results in a reduction in VE-cadherin protein and mRNA levels. Herein, we examined the mechanism(s) involved in the downregulation of VE-cadherin by CM. Human dermal microvascular EC exposed to CM showed a downregulation in VE-cadherin promoter activity and upregulation of Twist, Slug, and Snail expression. Reporter gene analysis demonstrated a direct repression of the VE-cadherin promoter by Slug, Snail, and Twist expression plasmids. At least two E-box motifs appear to be involved in this regulatory process as shown by electrophoretic mobility shift assays. These results suggest that factors released by breast cancer cells are able to upregulate Twist, Slug, and Snail expression in EC, which in turn downregulate the activity of the VE-cadherin promoter.
Dayami Lopez; Guilian Niu; Philippe Huber; W Bradford Carter
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-11-24
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  482     ISSN:  1096-0384     ISO Abbreviation:  Arch. Biochem. Biophys.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-03     Completed Date:  2009-02-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  United States    
Other Details:
Languages:  eng     Pagination:  77-82     Citation Subset:  IM    
Don and Erika Wallace Comprehensive Breast Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612-9416, USA.
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MeSH Terms
Antigens, CD / genetics*
Breast Neoplasms
Cadherins / genetics*
Carcinoma, Hepatocellular
Cell Line, Tumor
Culture Media, Conditioned
Endothelium, Vascular / physiology
Epithelial Cells / physiology
Gene Expression Regulation, Neoplastic
Genes, Reporter
Liver Neoplasms
Nuclear Proteins / genetics*
Promoter Regions, Genetic*
RNA, Messenger / genetics
Transcription Factors / genetics*
Transcription, Genetic
Twist Transcription Factor / genetics*
Reg. No./Substance:
0/Antigens, CD; 0/Cadherins; 0/Culture Media, Conditioned; 0/Nuclear Proteins; 0/RNA, Messenger; 0/TWIST1 protein, human; 0/Transcription Factors; 0/Twist Transcription Factor; 0/cadherin 5; 0/snail family transcription factors

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

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