Previous work from our laboratory suggest that oncogenic signals modulate glial differentiation. For example, activation of the protein kinase C will cause the C6 rat glioma cell line to lose the ability to increase glycerol phosphate dehydrogenase levels after glucocorticoid stimulation. One possible mechanism which would allow this to occur is by inhibiting the cell from increasing cAMP levels. We have found that elevated diacylglycerol levels (the natural ligand for the protein kinase C) causes inhibition of the beta-adrenergic and forskolin stimulated increased in cAMP levels in whole cells. This effect was not due to changes in phosphodiesterase levels or in beta-adrenegic receptor levels. We have also found that sodium butyrate inhibits the cell from increasing S-100 levels and this drug also interferes with the forskolin and beta-adrenergic response without influencing the phosphodiesterase levels. Therefore one common mechanism by which a cell is made to alter its differentiating program is through cAMP dependent mechanisms. We have also attempted to discern how cell shape alters the expression of differentiation. This is important since tumor cells do not spread or adhere as well as nontransformed cells. Primary culture of astrocytes do not synthesize as much glial fibrous acidic protein (GFAP), vimentin or actin when grown in suspension, or on collagen matrices. Human glioma cells also synthesize less of these proteins when grown as round cells. Therefore shape is an important factor in the expression of differentiation.
