The Role of Basic Fibroblast Growth Factor in Human Breast Cancer.

Although basic fibroblast growth factor bFGF is a classical mitogen and survival factor in fibroblasts and endothelial cells, it inhibits proliferation in breast cancer cells. We investigated the survival effects of bFGF in MCF-7 breast cancer cells to determine if this effect was also paradoxic. Our data confirmed that bFGF increased clonogenic survival of NIH 3T3 fibroblasts alone and prior to treatment with etoposide or 5-fluorouracil, two chemotherapeutic agents with different mechanisms of action, but decreased clonogenic survival of MCF-7 cells and increased their susceptibility to these chemotherapeutic agents in a dose and time dependent manner. Similarly, bFGF preincubation increased programmed cell death or apoptosis in these cells and was additive with the apoptotic effects of etoposide and 5-FU as determined by morphologic criteria and by DNA fragmentation assayed by 3-OH dUTP-FITC end labeling. These effects correlated with bFGF-induced decreases in Bcl-2 mRNA and protein levels and a decreased association of Bcl-2 with Bax in MCF-7 cells. These data suggest a role for bFGF in the susceptibility of breast cancer cells to chemotherapy-induced cell death.