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.