1998
DOI: 10.1073/pnas.95.7.3609
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Impact of oncogenes in tumor angiogenesis: Mutant K- ras up-regulation of vascular endothelial growth factor/vascular permeability factor is necessary, but not sufficient for tumorigenicity of human colorectal carcinoma cells

Abstract: Targeted disruption of the single mutant K-ras allele in two human colorectal carcinoma cell lines (DLD-1 and HCT-116) leads to loss of tumorigenic competence in nude mice with retention of ability to grow indefinitely in monolayer culture. Because expression of the mutant K-ras oncogene in these cell lines is associated with marked upregulation of vascular endothelial growth factor͞vascular permeability factor (VEGF͞VPF), we sought to determine whether this potent angiogenesis inducer plays a role in K-ras-de… Show more

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Cited by 236 publications
(133 citation statements)
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“…This contradiction may in part be explained by different methodology. On the other hand it is possible that VEGF alone is not sufficient for tumorigenicity of human colorectal carcinoma cells (Okada et al, 1998). Since other growth factors are also involved in angiogenesis processes (Carmeliet, 2000) it is likely that besides VEGF other molecules are needed to effectively promote tumour angiogenesis.…”
Section: Discussionmentioning
confidence: 99%
“…This contradiction may in part be explained by different methodology. On the other hand it is possible that VEGF alone is not sufficient for tumorigenicity of human colorectal carcinoma cells (Okada et al, 1998). Since other growth factors are also involved in angiogenesis processes (Carmeliet, 2000) it is likely that besides VEGF other molecules are needed to effectively promote tumour angiogenesis.…”
Section: Discussionmentioning
confidence: 99%
“…On the other hand, even a twofold change in the activity of the VEGF promoter may in itself have biological relevance. For example, 2 ± 3-fold reductions in VEGF expression in tumor cells have been shown to produce surprisingly profound suppressive e ects on tumor angiogenesis and tumor growth in vivo (Ferrara et al, 1996;Cheng et al, 1996;Okada et al, 1998;. In HPV-16-positive cells where other genetic and epigenetic changes (e.g.…”
Section: Hpv-16 E6 Oncoprotein and Vegf In Tumor Angiogenesismentioning
confidence: 99%
“…Taken together, the results suggest that the E6 oncoprotein may act as a transactivator of VEGF promoter activity. This function could contribute to its role in oncogenic transformation in vivo, given the importance of VEGF in tumor angiogenesis (Ferrara, 1995;Hanahan and Folkman, 1996;Okada et al, 1998) and the critical impact of angiogenesis on tumor growth in vivo (Hanahan and Folkman, 1996;Bouck et al, 1996).…”
Section: Hpv-16 E6 Oncoprotein and Vegf In Tumor Angiogenesismentioning
confidence: 99%
“…For example, IL8 has been shown to be a transcriptional target for ras signaling and its secretion is required for tumor-associated inflammation and angiogenesis in a human tumor xenograft model (Sparmann and Bar-Sagi, 2004). Ras has also been shown to mediate endothelial cell-dependent tumor angiogenesis via transcriptional upregulation of vascular endothelial growth factor (VEGF) and repression of thrombospondin (TSP-1) (Okada et al, 1998;Watnick et al, 2003). Ras alters the tumor microenvironment by inducing the expression of members of the matrix metalloproteinase (MMP) family (Ballin et al, 1988), which are capable of degrading basement membrane and other extracellular matrix (ECM) structures, allowing for tumor growth and invasion.…”
Section: Introductionmentioning
confidence: 99%