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 sp ite 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 biolog ical 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 regula tion of GS expression by the aforesaid hormone. Under this hormonal ac tion, changes in cell morphology occur and they are correlated with an overexpression of the GFAP, a marker of astroglial differentiation. O n the contrary, dibutyryl cyclic AMP (dbc AMP) down-regulates the GS-m RNA expression and decreases GS activity. These results suggest that G L-15 cells have a common glucocorticoid dependent mechanism able to in duce GS and GFAP as well as morphological changes. However in these ce lls AMPc responsive elements are involved in the negative modulation o f the GS expression, contrary to what occurs in normal astroglial cell s.