Normoxic and @entity519 regulation of XXXX ( @entity7 ) by @entity816 cells is mediated by Ras.

@entity1 @entity11349 @entity72757 @entity1313 @entity5 @entity7 @entity25897 @entity519 @entity816 @entity669 @entity463
@entity7 ( @entity7 ) has been identified as a key angiogenic factor involved in the growth and @entity5 . @entity463 ( @entity463 ) are the most common primary @entity1 @entity1313 , histo-pathologically characterized by intense @entity5 angiogenesis. GBMs do not harbour oncogenic Ras mutations, but there is a functional up-regulation of Ras signaling through activation of receptor @entity669 kinases overexpressed by these @entity5 . We demonstrate that Ras pathway activation regulates @entity7 secretion in @entity816 cell lines. Ras pathway inhibition was carried out using genetic and pharmacologic techniques. Astrocytoma cells that were transfected to express the dominant inhibitory mutant H-Ras(N17) demonstrated a reduction in @entity7 secretion under both normoxic and @entity519 conditions. Cells treated with the @entity11349 transferase inhibitor @entity72757 demonstrated similar reductions in @entity7 secretion. Furthermore, @entity816 cells expressing a constitutively phosphorylated and truncated EGF-R common in GBMs ( @entity25897 )) demonstrate further elevations in Ras activation, resulting in a further increase in @entity7 secretion. We have previously demonstrated that activation of Ras plays a vital role in transducing mitogenic signals in @entity1 @entity5 cells. Our present results further extend the role of Ras activation in modulating @entity5 angiogenesis in these @entity5 . We propose that Ras may contribute to the angiogenic switch in @entity816 .
