A TETRACYCLINE-RESPONSIVE PROMOTER SYSTEM REVEALS THE ROLE OF A SECRETED BINDING-PROTEIN FOR FGFS DURING THE EARLY PHASE OF TUMOR-GROWTH

We showed previously that a secreted binding protein for FGFs (BP) can induce tumor growth and angiogenesis of a non-tumorigenic human cell line (SW-13). To study the contribution of BP to different phases of t umor growth, we employed a regulated promoter system which is highly a ctive in SW-13 cells and can be downregulated >20-fold by treatment wi th tetracycline. We demonstrate that expression of BP in SW-13 cells ( SW-13/tetBP cells) induces colony formation in soft agar and tumor gro wth in athymic nude mice. Tetracycline downregulated BP expression in these cells and prevented their colony formation in soft agar. Continu ous tetracycline treatment of animals suppressed BP expression in tumo rs grown from SW-13/tetBP cells and reduced growth of the xenografts. Initiation of tetracycline treatment after xenograft tumors had been e stablished had no effect on further tumor expansion in spite of downre gulated BP levels. These data suggest that BP expression plays a role mainly in the early stages of tumor progression. (C) 1996 Academic Pre ss.