Expression of thrombospondin-1 in human hepatocarcinoma cell lines and its regulation by transcription factor Jun/AP-1

摘要: Thrombospondin-1 (TSP-1) is a homotrimeric glycoprotein synthesized in variety of normal and transformed cells, secreted into the extracellular matrix. Based on its known effects tumor endothelial TSP-1 was implicated growth metastasis. In present study, we have demonstrated expression human hepatocarcinoma cell lines. detected SK-HEP-1, Hep 3B immortalized liver Chang cells. Using two different lines, SK-HEP-1 studied phorbol 12-myristate 13-acetate (PMA) expression. synthesis stimulated by PMA both When cells were treated with PMA, mRNA started to increase at 30 min reached maximal level 6 h. induction completely inhibited pre-treatment 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), potent protein kinase C inhibitor. A promoter-luciferase reporter gene transcriptionally activated as well c-Jun. Among three putative AP-1 recognition sites promoter, deletion 1st 2nd caused loss PMA-induced up-regulation, while 3rd site showed no effect. subsequent experiments, recombinant c-Jun nuclear proteins induced stronger binding affinity for than ones. Our study that could be expressed hepatoma lines effectively regulated PMA. We also suggest activity through activation critical event consequently affects production processing protein.