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 tumor growth, we employed a regulated promoter system which is highly active in SW-13 cells and can be downregulated >20-fold by treatment with tetracycline. We demonstrate that expression of BP in SW-13 cells (SW-13/tetBP cells) induces colony formation in soft agar and tumor growth in athymic nude mice. Tetracycline downregulated BP expression in these cells and prevented their colony formation in soft agar. Continuous tetracycline treatment of animals suppressed BP expression in tumors grown from SW-13/tetBP cells and reduced growth of the xenografts. Initiation of tetracycline treatment after xenograft tumors had been established had no effect on further tumor expansion in spite of downregulated BP levels. These data suggest that BP expression plays a role mainly in the early stages of tumor progression.