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 cancer cells was studied in vitro. Exposure to bFGF resulted in significant growth inhibition, decreased DNA synthesis, and accumulation of cells in G0-G1. 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 stimulatory effects of 17beta-estradiol, insulin, or epidermal growth factor. Binding and cross-linking studies of 125I-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 Mr 142,000 (125)I-labeled bFGF cross-linked protein. Stimulation of MCF-7 cells with bFGF at concentrations which effected growth inhibition also resulted in activation of p42(mapk) (ERK2) and p44(mapk) (ERK1) mitogen-activated protein kinases. 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 inhibitory responses. Whether there is association between these phenomena remains unknown.
Fenig
E
E
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Wieder
R
R
Paglin
S
S
Wang
H
H
Persaud
R
R
Haimovitz-Friedman
A
A
Fuks
Z
Z
Yahalom
J
J
D001665:Binding Sites; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007457:Iodine Radioisotopes; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D007457:Iodine Radioisotopes; D016222:Fibroblast Growth Factor 2; D004247:DNA; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases