Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathways

The switch from a quiescent tumor to an invasive tumor is accompanied by the acquisition of angiogenic properties. This phenotypic change likely requires a change in the balance of angiogenic stimulators and angiogenic inhibitors. The nature of the angiogenic switch is not known. Here, we show that introduction of activated H-ras into immortalized endothelial cells is capable of activating the angiogenic switch. Angiogenic switching is accompanied by up-regulation of vascular endothelial growth factor and matrix metalloproteinase (MMP) bioactivity and down-regulation of tissue inhibitor of MMP. Furthermore, we show that inhibition of phosphatidylinositol-3-kinase leads to partial inhibition of tumor angiogenesis, thus demonstrating that activated H-ras activates tumor angiogenesis through two distinct pathways. Finally, we show evidence for two forms of tumor dormancy.

Ingår i:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences94:3, s. 861-8660027-8424
Ingår i:Proceedings of the National Academy of Sciences: Proceedings of the National Academy of Sciences94:3, s. 861-8661091-6490

Av författaren/redakt...: Arbiser, JL; Moses, MA; Fernandez, CA; Ghiso, N; Cao, YH; Klauber, N; visa fler...; Frank, D; Brownlee, M; Flynn, E; Parangi, S; Byers, HR; Folkman, J; visa färre...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.