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PMID: 7678836 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cyclic AMP distinguishes between two functions of acidic FGF in a rat bladder carcinoma cell line.

The Journal of cell biology ·Vol. 120 ·No. 3 ·1993-02-00 ·Pages 767-76

Boyer B, Thiery JP

Abstract

The rat bladder carcinoma cell line NBT-II exhibits two completely different responses to acidic FGF (aFGF): at high cell density, aFGF is a potent mitogen whereas at low cell density, aFGF acts as a scattering agent that can convert the epithelial NBT-II cells into fibroblastic-like, motile cells. The basis of the dual action of aFGF has been approached by using substances interfering with the transducing pathways known to be activated by growth factors. Genistein and tyrphostin, two inhibitors of tyrosine kinases, inhibit both cell scattering and mitogenesis induced by aFGF. Conversely, sodium orthovanadate, a potent inhibitor of tyrosine phosphatases can reproduce the two effects of aFGF, indicating that protein tyrosine phosphorylations are determinant in the two pathways. In contrast, transforming growth factor (TGF)-beta 1 is a strong inhibitor of DNA synthesis induced by aFGF but has no effect on cell scattering, providing evidence that the two pathways are divergent. In an attempt to determine the specificity of the pathways of aFGF we found that the level of cAMP, which can be externally elevated, is of pivotal importance in distinguishing between the two transducing pathways leading to either DNA replication or cell dispersion. Forskolin, 8-bromo cAMP, dibutyryl-cAMP, and cholera toxin are all capable of potentiating the mitogenic effect of aFGF while strongly inhibiting its scattering action. Moreover, addition of any of these substances to NBT-II cells converted into fibroblasts immediately induces their reversion towards an epithelial phenotype. These findings support a role for cAMP as a modulator of the effects of aFGF. Moreover, basal cAMP synthesis, which is not affected by aFGF, is higher in sparse than in dense cultures indicating that the level of cAMP depends on the status of the cell. Altogether, these results suggest that establishment and maintenance of the epithelial state require a precise regulation of cAMP level.

MeSH Terms
1-Methyl-3-isobutylxanthine/pharmacology 8-Bromo Cyclic Adenosine Monophosphate/pharmacology Animals Benzylidene Compounds/pharmacology Cell Division/drug effects Cholera Toxin/pharmacology Colforsin/pharmacology Cyclic AMP/metabolism DNA Replication/drug effects Fibroblast Growth Factor 1/pharmacology Genistein Isoflavones/pharmacology Kinetics Nitriles/pharmacology Protein-Tyrosine Kinases/antagonists & inhibitors,metabolism Rats Signal Transduction/drug effects Transforming Growth Factor beta/pharmacology Tumor Cells, Cultured Tyrphostins Urinary Bladder Neoplasms Vanadates/pharmacology Virulence Factors, Bordetella/pharmacology
Chemicals
Benzylidene Compounds Isoflavones Nitriles Transforming Growth Factor beta Tyrphostins Virulence Factors, Bordetella Fibroblast Growth Factor 1 Colforsin 8-Bromo Cyclic Adenosine Monophosphate Vanadates Cholera Toxin Genistein Cyclic AMP Protein-Tyrosine Kinases tyrphostin A23 1-Methyl-3-isobutylxanthine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Boyer B
Laboratoire de Physiopathologie du Développement, Unité de Recherche Associée 1337 Cenre National de la Recherche Scientifique, Ecole Normale Supérieure, Paris, France.
Thiery J P
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.120.3.767
Published
1993-02-00
Pages
767-76
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2119551
Subset
IM
Grants
NCI NIH HHS · 1 RO1 CA49417-01 A3 · United States
External Links
PubMed source DOI: 10.1083/jcb.120.3.767 PMC Full Text View journal details
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