VE-cadherin expression and clustering maintain low levels of survivin in endothelial cells

Am J Pathol. 2004 Jul;165(1):181-9. doi: 10.1016/S0002-9440(10)63287-7.

Abstract

Survivin is strongly expressed in embryonic organs and in tumor cells but is low or absent in differentiated normal tissues. Resting endothelium expresses low levels of survivin but can up-regulate its synthesis on activation to proliferate. The mechanisms responsible for survivin down-regulation in resting conditions are still unknown. We report here that confluence and vascular endothelial-cadherin (VE-cadherin) expression induce contact inhibition of cell growth and survivin down-regulation in the endothelium. Using beta-catenin null and positive isogenic endothelial cell lines we found that the effect requires beta-catenin expression and its association to VE-cadherin cytoplasmic tail. Furthermore, in allantois organ cultures, survivin expression is up-regulated in areas of growing vessels where VE-cadherin is partially dismantled from junctions or in VE-cadherin -/- specimens. Overall, these data indicate that VE-cadherin and beta-catenin may negatively regulate survivin synthesis in endothelial cells. Consistently, in epidermal and pancreatic cell lines or ovarian tumors, epithelial-cadherin (E-cadherin) and survivin expression is inversely related, suggesting a non-cell-specific role of cadherins in reducing survivin synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allantois / cytology
  • Animals
  • Antigens, CD
  • Blotting, Western
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Division
  • Cell Line
  • Cell Line, Tumor
  • Cluster Analysis
  • Cytoskeletal Proteins
  • Down-Regulation
  • Embryo, Mammalian
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Fibronectins / metabolism
  • Gene Expression Regulation, Developmental
  • Green Fluorescent Proteins
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Luminescent Proteins
  • Mice
  • Mice, Knockout
  • Microscopy, Confocal
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Neoplasm Proteins
  • Neovascularization, Physiologic / physiology
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Stem Cells / cytology
  • Survivin
  • Trans-Activators
  • Umbilical Veins / cytology
  • Up-Regulation
  • beta Catenin

Substances

  • Antigens, CD
  • BIRC5 protein, human
  • CTNNB1 protein, human
  • CTNNB1 protein, mouse
  • Cadherins
  • Cytoskeletal Proteins
  • Fibronectins
  • Inhibitor of Apoptosis Proteins
  • Luminescent Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Survivin
  • Trans-Activators
  • beta Catenin
  • cadherin 5
  • Green Fluorescent Proteins