Basic fibroblast growth factor confers growth inhibition and mitogen-activated protein kinase activation in human breast cancer cells Journal Article
| Authors: | Fenig, E.; Wieder, R.; Paglin, S.; Wang, H.; Persaud, R.; Haimovitz-Friedman, A.; Fuks, Z.; Yahalom, J. |
| Article Title: | Basic fibroblast growth factor confers growth inhibition and mitogen-activated protein kinase activation in human breast cancer cells |
| Abstract: | 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. |
| Keywords: | epidermal growth factor; mitogen activated protein kinase; controlled study; human cell; dna synthesis; cell cycle; cell division; breast cancer; cell line; enzyme activation; in vitro study; tumor cells, cultured; breast neoplasms; fibroblast growth factor 2; dna; cell culture; iodine radioisotopes; insulin; binding sites; estradiol; mitogen-activated protein kinases; drug binding; mitogen-activated protein kinase 1; mitogen-activated protein kinase 3; growth inhibitors; ca(2+)-calmodulin dependent protein kinase; humans; human; priority journal; article; recombinant fibroblast growth factor; calcium-calmodulin-dependent protein kinases |
| Journal Title: | Clinical Cancer Research |
| Volume: | 3 |
| Issue: | 1 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1997-01-01 |
| Start Page: | 135 |
| End Page: | 142 |
| Language: | English |
| PUBMED: | 9815549 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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