EFFECTS OF BASIC FIBROBLAST GROWTH-FACTOR ON THE DIFFERENTIATION, GROWTH, AND VIABILITY OF A NEW HUMAN MEDULLOBLASTOMA CELL-LINE (UM-MB1)

We presently report the effects of human recombinant basic fibroblast growth factor (bFGF) on a newly established medulloblastoma cell line, UM-MB1, This predominantly adherent cell line has a mean doubling tim e of 39.3 hours and was found, by karyotypic analysis, to be near trip loid. UM-MB1 consists of undifferentiated cells expressing markers of neuronal lineage such as the three neurofilament subunits as well as n euron-specific enolase, synaptophysin, and microtubule-associated prot eins 1 and 5, In contrast, no immunoreactivity for glial fibrillary ac idic protein was evident. When exposed to nanomolar amounts of bFGF, U M-MB1 cells began to extend neurite-like processes with arborizations and growth-cone-like structures, In addition, UM-MB1 cells treated wit h bFGF exhibited ultrastructural alterations that reflect their enhanc ed differentiation as well as the Increased expression of at least one of the neurofilament subunits as evidenced both immunocytochemically and on Western blots. Furthermore, bFGF significantly decreased UM-MB1 cell growth as well as Induced their death, UM-MB1 cells treated with bFGF for several days displayed DNA cleavage, nuclear shrinkage, and chromatin condensation while retaining their cytoplasmic and mitochond rial membrane integrity, all early indices of apoptosis, After this, c ell death was evident with the concomitant appearance of the classical apoptotic bodies. By how cytometry, bFGF was found to increase the pr oportion of cells in G1 before inducing their death by apoptosis, In c onclusion, UM-MB1 tells can, when appropriately stimulated, be induced to differentiate along their neuronal lineage pathway. Their differen tiation induced by bFGF, although incomplete, appears to promote or in hibit the expression of apoptotic effectors or suppressors in these ce lls, respectively, so to induce their death by an apoptotic-like mecha nism.