Tumor-induced upregulation of Twist, Snail, and Slug represses the activity of the human VE-cadherin promoter

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 24 h results in a reduction in VE-cadhe...

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Bibliographic Details
Published in:Archives of biochemistry and biophysics 2009-02, Vol.482 (1), p.77-82
Main Authors: Lopez, Dayami, Niu, Guilian, Huber, Philippe, Carter, W. Bradford
Format: Article
Language:English
Subjects:
Antigens, CD - genetics
Breast cancer cells
Breast Neoplasms
Cadherins - genetics
Carcinoma, Hepatocellular
Cell Line, Tumor
Culture Media, Conditioned
Endothelial cells
Endothelium, Vascular - physiology
Epithelial Cells - physiology
Female
Gene Expression Regulation, Neoplastic
Genes, Reporter
Humans
Liver Neoplasms
Nuclear Proteins - genetics
Plasmids
Promoter
Promoter Regions, Genetic
Repressors
RNA, Messenger - genetics
Slug
Snail
Snail Family Transcription Factors
Transcription Factors - genetics
Transcription, Genetic
Transcriptional regulation
Transfection
Twist
Twist-Related Protein 1 - genetics
VE-cadherin
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Summary: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 24 h 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.
ISSN:0003-9861
1096-0384
DOI:10.1016/j.abb.2008.11.016