BASIC FIBROBLAST GROWTH-FACTOR CONFERS GROWTH-INHIBITION AND MITOGEN-ACTIVATED PROTEIN-KINASE ACTIVATION IN HUMAN BREAST-CANCER CELLS

The effect of basic fibroblast growth factor (bFGF) on human breast ca ncer cells was studied in vitro, Exposure to bFGF resulted in signific ant growth inhibition, decreased DNA synthesis, and accumulation of ce lls in G(0)-G(1). The IC50 for growth inhibition in MCF-7 cells was 50 pg/ml, and it was abrogated by neutralizing antibodies against bFGF, Inhibition of growth by bFGF was predominant over the growth stimulato ry effects of 17 beta-estradiol, insulin, or epidermal growth factor, Binding and cross-linking studies of I-125-labeled bFGF in intact MCF- 7 cells demonstrated 5.2 x 10(3) saturable bFGF binding sites per cell , a dissociation constant of 57 pM, and a M-r 142,000 I-125-labeled bF GF cross-linked protein, Stimulation of MCF-7 cells with bFGF at conce ntrations which effected growth inhibition also resulted in activation of p42(mapk) (ERK2) and p44(mapk) (ERK1) mitogen-activated protein ki nases, These data demonstrate that whereas bFGF inhibits the growth of several breast cancer cell lines, it concomitantly activates ERK1 and ERK2, generally considered to signal mitogenic rather than growth inh ibitory responses, Whether there is association between these phenomen a remains unknown.