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Biochem Biophys Res Commun. 1999 Jan 19;254(2):480-3.

Oncogenic ras fails to restore an in vivo tumorigenic phenotype in embryonic stem cells lacking vascular endothelial growth factor (VEGF).

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Department of Cardiovascular Research, Genentech, Inc., 1 DNA Way, South San Francisco, California, 94080, USA.


Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis. Previous studies have shown that the ability of murine embryonic stem (ES) cells to form teratocarcinomas in nude mice is substantially reduced following targeted inactivation of the VEGF gene. We sought to determine whether VEGF-/- ES cells' tumorigenic phenotype can be rescued by transfection with a mutant H-ras. VEGF-/- ES cells were transfected with expression vector which directs the constitutive synthesis of oncogenic Val-12 ras. Expression of ras protein was documented by Western blot analysis. We injected several clones with different levels of Val-12 ras expression in nude mice. In agreement with our earlier report, VEGF-/- ES cells formed much smaller tumors than control ES cells. However, none of the ras-expressing clones tested formed tumors larger than those derived from parental VEGF-/- cells. Thus, pluripotent cells such as ES cells are unable to compensate for the loss of VEGF even in the presence of a potent oncogenic stimulus such as mutant ras. These findings strengthen the hypothesis that VEGF-mediated angiogenesis is crucial for effective in vivo tumor growth.

[Indexed for MEDLINE]

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