稳定表达组织因子的黑色素瘤细胞中血管内皮细胞生长因子的诱导

Induction of vascular endothelial cell growth factor from melanoma cells that stably express tissue factor

研究黑色素瘤细胞中多种信号传导途径的特异抑制剂与组织因子诱导血管内皮生长因子的关系 ,发现只有P4 4 /42MAPK激酶特异的抑制剂PD980 5 9对VEGF的表达有抑制效应。MAPK激酶的Westernblot检测表明PD980 5 9完全抑制了组织因子稳定表达细胞的磷酸化的P4 4 /42MAPK激酶的表达 ,说明黑色素瘤细胞中组织因子通过P4 4 /42MAPK激酶途径诱导VEGF的表达。通过对VEGF的启动子区的不同片段对报告基因表达的研究表明 ,稳定表达组织因子的黑色素瘤细胞中VEGF启动子的活性可能部分依赖于转录因子AP

To study the singaling pathway by which the tissue factor(TF) induces the expression of vascular endothelial cells growth factor(VEGF) in melanoma cells. Using several singal pathway inhibitors, PD98059, staurosporine, GF109203×, Wortmannin, Genistein, AFC, H 7, it was found that only special inhibitor of P44/42 MAP kinase kinase (MAPKK) PD98059 inhibited the expression of VEGF. Western blot result proved that PD98059 distinctively inhibit the phospho P44/42 MAP kinase. In the melanoma cells the indution proceed of TF to VEGF by TF was related to P44/42 MAP kinase signal pathway. The region from -790 to -451 played an important role for VEGF expression in the stably transfected melanoma cells by TF. In this region there was a binding site for transcription factor AP 1. This transcription factor might be essential for TF to induce VEGF expression.