PMID- 9815549 OWN - NLM STAT- MEDLINE DCOM- 19990216 LR - 20091119 IS - 1078-0432 (Print) IS - 1078-0432 (Linking) VI - 3 IP - 1 DP - 1997 Jan TI - Basic fibroblast growth factor confers growth inhibition and mitogen-activated protein kinase activation in human breast cancer cells. PG - 135-42 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 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. FAU - Fenig, E AU - Fenig E AD - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. FAU - Wieder, R AU - Wieder R FAU - Paglin, S AU - Paglin S FAU - Wang, H AU - Wang H FAU - Persaud, R AU - Persaud R FAU - Haimovitz-Friedman, A AU - Haimovitz-Friedman A FAU - Fuks, Z AU - Fuks Z FAU - Yahalom, J AU - Yahalom J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Clin Cancer Res JT - Clinical cancer research : an official journal of the American Association for Cancer Research JID - 9502500 RN - 0 (Growth Inhibitors) RN - 0 (Iodine Radioisotopes) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - 9007-49-2 (DNA) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Binding Sites MH - Breast Neoplasms/enzymology/*metabolism MH - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism MH - Cell Cycle/drug effects MH - Cell Division/drug effects MH - DNA/biosynthesis/drug effects MH - Enzyme Activation MH - Fibroblast Growth Factor 2/antagonists & inhibitors/*pharmacology MH - Growth Inhibitors/pharmacology MH - Humans MH - Iodine Radioisotopes MH - Mitogen-Activated Protein Kinase 1 MH - Mitogen-Activated Protein Kinase 3 MH - *Mitogen-Activated Protein Kinases MH - Tumor Cells, Cultured EDAT- 1997/01/01 00:00 MHDA- 1998/11/17 00:01 CRDT- 1997/01/01 00:00 PHST- 1997/01/01 00:00 [pubmed] PHST- 1998/11/17 00:01 [medline] PHST- 1997/01/01 00:00 [entrez] PST - ppublish SO - Clin Cancer Res. 1997 Jan;3(1):135-42.