FIBROBLAST GROWTH-FACTOR-2 AND THE PROTEASE ACTIVITY OF TUMOR-CELLS ISOLATED FROM BK VIRUS TAT TRANSGENIC MICE/

In BK virus (BKV)/tat transgenic mice, the relatively low incidence an d long latency period of tumors indicate that the BKV/tat transgene is not sufficient for the expression of a complete oncogenic phenotype. Since angiogenesis and the production of proteases are critical for tu mor growth, we evaluated the expression of two potent angiogenic molec ules, fibroblast growth factor type 2 (FGF-2), and hepatocyte growth f actor (HGF), and of the fibrinolytic system in cell lines isolated fro m tumors of different histotypes developed by BKV/tattransgenic mice. Here we show that the overexpression of HGF is a unique feature of spi ndle cells derived from murine Kaposi's sarcoma-like lesions, whereas FGF-2 is detectable in all the cell lines tested. Interestingly, FGF-2 is secreted only by adenocarcinoma-derived T53 cells that show a full y transformed phenotype in vitro. In addition, T53 cells synthesize la rger amounts of urokinase-type plasminogen activator (uPA) than the ot her cell lines studied. This is due to the secretion of FGF-2 and not to the presence of extracellular Tat. We conclude that the high levels of expression of uPA and its receptor, and the very low levels of pla sminogen activator inhibitor type 1, may contribute to the tumorigenic phenotype of T53 cells.