The integrin αvβ2 a cell surface adhesion receptor that has been reported to mediate tumor angiogenesis. Angiotensin II, also plays a role in formation of new blood vessels in animal models by mechansims that remain unknown. We tested the role of Angiotensin II to regulate integrin expression m culiured human umbilical vein endothelial cells (HUVECS). The cells were treated with Angiotensin II (5×10-8 M) for at least 5 hours, along with vehicle treated controls. Both sets of cells were then analyzed for expression of the αv subunit of the integrin αvβ3 by Northern analysis. There was a significant increase in the level of αv mRNA in the cells treated with the peptide hormone. The effects of Angiotensin il were then tested on other cell lines that had been transfected with recombinant constructs containing regions of the αv promoter fused to the luciferase reporter gene. The constructs contained integrated copies of the promoter-reporter gene in 2 different cell lines, Ros 106 (rat osteosarcoma cells) and G292 ( human breast carcinoma cells). At least 3 independent integrations in each of the 2 cell lines were tested for the effect ot Angiotensin II on Uy promoter driven luciferase expression. Once again, all cells treated with the peptide hormone showed an increase of promoter activity after treatment with Anjjotensin II (5×10-8 M). This result may implicate a step in the molecular mechanism of action of Angiotensin II as an angiogenic agent.
|State||Published - Dec 1 1996|