TY - JOUR
T1 - Basic fibroblast growth factor confers growth inhibition and mitogen-activated protein kinase activation in human breast cancer cells
AU - Fenig, Eyal
AU - Wieder, Robert
AU - Paglin, Shoshana
AU - Wang, Huisheng
AU - Persaud, Roger
AU - Haimovitz-Friedman, Adriana
AU - Fuks, Zvi
AU - Yahalom, Joachim
PY - 1997
Y1 - 1997
N2 - 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 17β-estradiol, insulin, or epidermal growth factor. Binding and cross-linking studies of 125I-labeled bFGF in intact MCF-7 cells demonstrated 5.2 x 103 saturable bFGF binding sites per cell, a dissociation constant of 57 pM, and a M(r) 142,000 125I-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.
AB - 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 17β-estradiol, insulin, or epidermal growth factor. Binding and cross-linking studies of 125I-labeled bFGF in intact MCF-7 cells demonstrated 5.2 x 103 saturable bFGF binding sites per cell, a dissociation constant of 57 pM, and a M(r) 142,000 125I-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.
UR - http://www.scopus.com/inward/record.url?scp=0031041971&partnerID=8YFLogxK
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C2 - 9815549
AN - SCOPUS:0031041971
SN - 1078-0432
VL - 3
SP - 135
EP - 142
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 1
ER -