THE ROLE OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR IN HUMAN GLIOMAS .2.THE CONTROL OF GLIAL PROCESS EXTENSION AND THE EXPRESSION OF GLIAL FIBRILLARY ACIDIC PROTEIN

Our earlier investigations of the biology of the epidermal growth fact or receptor (EGFR) in human gliomas demonstrated that the level of EGF R expression did not directly predict the glioma growth response to EG F, suggesting that the function of the EGFR in glioblastomas might not be limited to mediating the growth effects of EGF. We conducted the c urrent studies to investigate the function(s) of the EGFR not related to growth control in human gliomas. These investigations show that the EGFR mediates the stimulative effects of EGF on glial process extensi on and glial fibrillary acidic protein (GFAP) expression. in addition, the level of EGFR expression correlates inversely with glioma cell re sponsiveness to differentiation promoting agents (for example, nerve g rowth factor and transforming growth factor-beta) that act through tra nsmembrane tyrosine kinase receptors. Thus, glioma lines with a high l evel of EGFR expression (for example, T-98G cells) responded to fewer differentiation promoting factors than lines with a low level of EGFR expression (such as U-373MG cells). Our results suggest that the EGFR in gliomas may participate in mediating the process extension and GFAP stimulative effects of both EGF and other differentiation promoting a gents. These properties represent components of the differentiated sta te in glia because their expression is stimulated by dibutyryl cyclic adenosine monophosphate in normal astrocytes. The involvement of the E GFR in the expression of these glial specific properties suggests that the EGFR may play an important role in glial differentiation.