H-Ras is a negative regulator of alpha3beta1 integrin expression in ECV304 endothelial cells

Biochem Biophys Res Commun. 1999 Apr 2;257(1):95-9. doi: 10.1006/bbrc.1999.0302.

Abstract

We have examined the role of Ras in integrin expression in ECV304 endothelial cells. Among the integrins examined in stable ECV304 transfectants expressing dominant active H-Ras (DAR-ECV), expression of alpha3beta1 integrin showed a prominent reduction in all the DAR-ECV clones when compared to the parental ECV304 cells. This implies that H-Ras negatively regulates the expression of alpha3beta1 integrin in ECV304 cells. When treated with inhibitors of the Ras downstream pathway (LY294002, PD98059, SB203580), the expression of alpha3beta1 integrin was up-regulated most significantly by LY294002, suggesting that among the downstream pathways of Ras, phosphatidylinositol 3-kinase is a major determinant. With the application of blocking antibody to alpha3beta1 integrin (2 - 2 x 10(4) nM), migration of ECV304 cells was enhanced to maximal (18%) at 20 nM. These results suggest that migration of endothelial cells could be modulated by H-Ras via alteration of the expression levels of alpha3beta1 integrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / pharmacology
  • Cell Line, Transformed
  • Cell Movement / drug effects
  • Chromones / pharmacology
  • Dose-Response Relationship, Drug
  • Down-Regulation* / drug effects
  • Endothelium / cytology
  • Endothelium / drug effects
  • Endothelium / enzymology
  • Endothelium / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / pharmacology
  • Flow Cytometry
  • Genes, Dominant / genetics
  • Humans
  • Imidazoles / pharmacology
  • Integrin alpha3beta1
  • Integrins / immunology
  • Integrins / metabolism*
  • Morpholines / pharmacology
  • Oncogene Protein p21(ras) / antagonists & inhibitors
  • Oncogene Protein p21(ras) / genetics
  • Oncogene Protein p21(ras) / metabolism*
  • Phenotype
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Pyridines / pharmacology
  • Signal Transduction / drug effects
  • Transfection
  • Up-Regulation / drug effects

Substances

  • Antibodies
  • Chromones
  • Enzyme Inhibitors
  • Flavonoids
  • Imidazoles
  • Integrin alpha3beta1
  • Integrins
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Pyridines
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Oncogene Protein p21(ras)
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one