Abstract | BACKGROUND: HER2 overexpression imparts a metastatic advantage in breast cancer. We have shown that HER2 signaling in breast cancer cells induces adjacent endothelial cell (EC) retraction, disrupting endothelial integrity. Because endothelial integrity is dependent on the adherens junctions, we postulated that the mechanism of tumor cell-induced EC retraction involves dissociation of catenin proteins from vascular endothelial ( VE) cadherin. In this study, we report a loss of VE-cadherin in tumor-associated EC. We also tested for a change of catenin dissociation from VE-cadherin by manipulating HER2 signaling in tumor cells. METHODS: RESULTS: CONCLUSIONS: Our data suggest that HER2 induction of EC retraction involves both down-regulation of VE-cadherin and dissociation of catenins. HER2 signaling appears to regulate this potential metastatic mechanism. Further, Src phosphorylation suggests that this pathway may be involved in this mechanism.
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Authors | W Bradford Carter, Guilian Niu, Michael D Ward, Gregory Small, Julianne E Hahn, Barbara J Muffly |
Journal | Annals of surgical oncology
(Ann Surg Oncol)
Vol. 14
Issue 10
Pg. 2971-8
(Oct 2007)
ISSN: 1068-9265 [Print] United States |
PMID | 17593333
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Cadherins
- Catenins
- Culture Media, Conditioned
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Topics |
- Blotting, Western
- Breast Neoplasms
(genetics, pathology)
- Cadherins
(metabolism)
- Catenins
(metabolism)
- Cell Line, Tumor
- Cell Transformation, Neoplastic
(genetics, pathology)
- Culture Media, Conditioned
- Down-Regulation
(physiology)
- Endothelial Cells
(pathology)
- Female
- Gene Expression Regulation, Neoplastic
(physiology)
- Genes, erbB-2
(genetics)
- Humans
- In Vitro Techniques
- Signal Transduction
(genetics)
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