The up-regulation of vascular endothelial growth factor in mutated Ha-ras HaCaT cell lines is reduced by a farnesyl transferase inhibitor.
The induction of tumor angiogenesis is mediated in particular by an increased production of VEGF. As ras oncogene is implicated in tumorigenesis, the inhibition of farnesyl transferase activity has recently been developed. The purpose of this study was to evaluate whether expression of mutated Ha-ras oncogene is associated with an altered expression of VEGF in an in vitro model of human skin carcinogenesis and to appreciate the effect of a new farnesyl transferase inhibitor on this VEGF expression. The amounts of VEGF secreted by an HaCaT cell line and two cell clones (metastatic or not) obtained after mutated c-Ha-ras transfection were compared. Our findings showed that the release of VEGF is greater for HaCaT-ras than for HaCaT cells and could be down-regulated using a protein farnesyl transferase inhibitor, in a reversible and dose-dependent manner. These results confirm that the Ha-ras oncogene can contribute to tumor development and progression of epidermal tumors through neoangiogenesis and that farnesyl transferase inhibitors as anticancer drugs may be efficient for the reduction of skin tumor growth.
Charvat
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S
Laboratoire de recherche Peau humanie et immunite, INSERM 346, Hôpital Edouart Herriot, Lyon, France.
Duchesne
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M
Parvaz
P
P
Chignol
M C
MC
Schmitt
D
D
Serres
M
M
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D002460:Cell Line; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D011905:Genes, ras; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D008222:Lymphokines / Q000096:biosynthesis*; D009154:Mutation; D015398:Signal Transduction; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase