Distinctive effects of rat fibroblast growth factor-2 isoforms on PC12 and Schwann cells

• Published in: Growth factors (Chur, Switzerland) Vol. 19; no. 3; p. 175
• Main Authors: Müller-Ostermeyer, F, Claus, P, Grothe, C
• Format: Journal Article
• Language: English
• Published: England 2001
• Subjects: Animals; Cell Division; Cell Survival; Fibroblast Growth Factor 2 - chemistry; Fibroblasts - metabolism; PC12 Cells; Plasmids - metabolism; Protein Binding; Protein Isoforms; Protein-Tyrosine Kinases; Rats; Receptor Protein-Tyrosine Kinases - biosynthesis; Receptor, Fibroblast Growth Factor, Type 1; Receptor, Fibroblast Growth Factor, Type 3; Receptor, Fibroblast Growth Factor, Type 4; Receptors, Fibroblast Growth Factor - biosynthesis; Recombinant Proteins - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Schwann Cells - metabolism; Transfection
• ISSN: 0897-7194
• DOI: 10.3109/08977190109001085

Fibroblast growth factor-2 (FGF-2) is an important modulator of cell growth and differentiation and stimulates cell survival of various cells including neurons. Rat FGF-2 occurs in three isoforms, a low molecular weight 18 kD and two high molecular weight forms (21, 23 kD), representing alternative translation products from a single mRNA. The 18 kD isoform shows mainly cytoplasmatic localization, whereas the 21/23 kD FGF-2 are localized in the nucleus. In addition, the FGF-2 isoforms are differentially regulated in the sensory ganglia and peripheral nerve following nerve injury and in the adrenal medulla during post-natal development and after hormonal stimuli. The distinct intracellular distribution and differential regulation of the different FGF-2 isoforms indicate that they have unique biological roles, however, little is known about the biological effects of the high molecular weight FGF-2 isoforms. Immortalized Schwann cells and PC12 cells, which stably overexpress the different FGF-2 isoforms, showed that the different endogenous-overexpressed FGF-2 isoforms lead to dramatic modifications in cell proliferation and survival, when tested in serum-free and serum-containing medium. In contrast, application of recombinant FGF-2 isoforms on normal PC12 and immortalized Schwann cells results in similar biological effects on the proliferation and survival of the cells. Furthermore, we investigated the potential regulatory effects of endogenous-overexpressed and exogenous-applied FGF-2 isoforms on the mRNA level of the FGF-2 receptors and, additionally, on the tyrosin hydroxylase mRNA expression in PC12 cells.