Glutamine synthetase gene expression in a glioblastoma cell-line of clonal origin : regulation by dexamethasone and dibutyryl cyclic AMP

We investigated the expression of glutamine synthetase (GS), an enzyme involved in astroglial metabolism and marker of astroglial functional maturity, in a glioblastoma cell-line (GL-15) of clonal origin. In spite of their phenotypic immaturity, evidenced in a mosaic fashion by a poor glial fibrillary acidic protein (GFAP) expression, the level of GS-mRNA is high in GL15 cells and the considerable amount of GS biological activity can be further induced and stabilized by glucocorticoids. A correlation between the induction by dexamethasone of the GS-mRNA level and the GS biological activity suggests a transcriptional regulation of GS expression by the aforesaid hormone. Under this hormonal action, changes in cell morphology occur and they are correlated with an overexpression of the GFAP, a marker of astroglial differentiation. On the contrary, dibutyryl cyclic AMP (dbc AMP) down-regulates the GS-mRNA expression and decreases GS activity. These results suggest that GL-15 cells have a common glucocorticoid dependent mechanism able to induce GS and GFAP as well as morphological changes. However in these cells AMPc responsive elements are involved in the negative modulation of the GS expression, contrary to what occurs in normal astroglial cells.