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Journal of Neuroscience, Vol 7, 3639-3653, Copyright © 1987 by Society for Neuroscience
Acidic and basic fibroblast growth factors promote stable neurite outgrowth and neuronal differentiation in cultures of PC12 cells
RE Rydel and LA Greene
Department of Pharmacology, New York University School of Medicine, New York 10016.
Acidic (aFGF) and basic (bFGF) fibroblast growth factors are well-
characterized peptide hormones that have potent angiogenic activity and
that are mitogenic for a variety of cell types. The present findings
demonstrate that FGFs can reproduce the entire spectrum of rat
pheochromocytoma PC12 cell responses previously shown to be elicited by
NGF. These include responses that are rapid (cell flattening, enhanced
phosphorylation of tyrosine hydroxylase) or delayed (neurite outgrowth,
induction of phosphorylated MAP 1.2, regulation of NILE and Thy-1
glycoproteins, cessation of mitosis, elevation of AChE activity), as well
as responses that have been shown to be either transcription- independent
(neurite regeneration, promotion of survival) or transcription-dependent
(priming, regulation of NILE and Thy-1 glycoproteins, elevation of AChE
activity). The only responses for which the FGFs and NGF consistently
showed quantitative differences were in the rates for neurite initiation
and elongation in serum- containing medium. Thus, while all 3 factors
promoted the formation of stable neurites, the network of outgrowth
elicited by NGF at any given time of treatment was always of greater
density. Togari et al. (1985) have previously reported that bFGF can
initiate transient neurite formation in PC12 cell cultures. The present
observations describe a variety of additional actions of bFGF on a neuronal
cell line, and demonstrate that aFGF is capable of mimicking many, if not
all, of these actions. These observations thus extend the range of actions
that aFGF and bFGF may potentially exert on nerve cells, either during
their development, repair, or maintenance. In addition, this work suggests
that the PC12 cell line may serve as a useful model system with which to
study the mechanism of action of FGFs on neurons. Since all 3 factors
appear capable of eliciting the same wide spectrum of responses, molecular
events specifically associated with FGFs and NGF in PC12 cells may prove
illuminating of the causal steps involved in neuronal differentiation.
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