PKA AND PKC ACTIVATION INDUCES OPPOSITE GLIAL FIBRILLARY ACIDIC PROTEIN (GFAP) EXPRESSION AND MORPHOLOGY CHANGES IN A GLIOBLASTOMA MULTIFORM CELL-LINE ELF CLONAL ORIGIN

Possible differentiation mechanisms were investigated in a glioblastom a multiform cell line (GL15) presenting an undifferentiated phenotype with weak glial fibrillary acidic protein (GFAP) and strong vimentin ( VIM) expression, Serum-free conditions induced time-dependent increase s of GFAP-mRNA and GFAP protein levels, associated with a process-bear ing astrocytic morphology. Activation of protein kinase C (PKC) by tum or promoter phorbol 12-myrystate 13-acetate (PMA) induced a rapid morp hological differentiation and a decrease in GFAP mRNA, whereas the GFA P level remained unchanged. Such parameters were shown to characterize a physiological differentiation stage in astroglial cultures, Treatme nt of process-bearing GL15 cells with dibutyryl cyclic AMB (dbcAMP), a protein kinase A (PKA) activator, induced a time-dependent decrease i n the GFAP mRNA and GFAP protein levels and reverted morphological cha nges induced by serum-free conditions. Neither PMA nor dbcAMP influenc ed the VIM mRNA expression. In GL15 cells, PKC and PKA activation have opposite effects. Understanding the role of these kinases in malignan t transformation and in the in vitro differentiation process is of bot h basic and clinical interest. (c) 1995 Wiley-Liss, Inc.