title: H-Ras is a negative regulator of alpha3beta1 integrin expression in ECV304 endothelial cells.
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.
authors: Department of Biochemistry, College of Medicine, Cheongju, Korea.
authors: E Y
authors: EY
authors: Shin
authors: J Y
authors: JY
authors: Lee
authors: M K
authors: MK
authors: Park
authors: G B
authors: GB
authors: Jeong
authors: E G
authors: EG
authors: Kim
authors: S Y
authors: SY
authors: Kim
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D002461:Cell Line, Transformed; D002465:Cell Movement / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D039201:Integrin alpha3beta1; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D015689:Oncogene Protein p21(ras) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000906:Antibodies; D002867:Chromones; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D039201:Integrin alpha3beta1; D016023:Integrins; D009025:Morpholines; D015689:Oncogene Protein p21(ras); D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one