Over-expression of the 18 kD and 21/23 kD fibroblast growth factor-2 isoforms in PC12 cells and Schwann cells results in altered cell morphology and growth.

Basic fibroblast growth factor (FGF-2) occurs in different isoforms which represent alternative translation products from a single mRNA. The question of whether the presence of multiple FGF-2 isoforms has physiological implications is compelling but unresolved so far. However, it has been shown recently that the FGF-2 isoforms are differentially regulated in sensory ganglia and peripheral nerve following nerve injury and, moreover, in the adrenal medulla during postnatal development and after hormonal stimuli suggesting that the isoforms may serve different physiological functions. To investigate isoform-specific effects we have established immortalized Schwann cells and PC12 cells stably over-expressing the 18 kD and the HMW isoforms. We found that the over-expression of the different isoforms alters morphology and growth of the Schwann cells. PC12 cells over-expressing the 18 kD FGF-2 were found to differentiate towards the neuronal phenotype whereas over-expression of the HMW isoforms resulted in a stabilization of the endocrine phenotype. Taken together, these data corroborate the idea of FGF-2 isoform-specific functions.