J. Gomez et al., OVEREXPRESSION OF THE NEURON-SPECIFIC MOLECULE BM88 IN MOUSE NEUROBLASTOMA-CELLS - ALTERED RESPONSIVENESS TO GROWTH-FACTORS, Journal of neuroscience research, 51(1), 1998, pp. 119-128
Previous studies have shown that the BM88 antigen, a novel neuron-spec
ific molecule, promotes the differentiation of mouse neuroblastoma (Ne
uro 2a) cells. In particular, stably transfected, with the BM88 cDNA,
Neuro 2a cells overexpressing the BM88 antigen (Neuro2a-BM88 cells) ar
e morphologically distinct from the nontransfected Neuro 2a cells; the
y exhibit enhanced process outgrowth and a slower rate of division. In
this study we used Neuro2a and the morphologically differentiated Neu
ro 2a-BM88 cells to compare their responsiveness to growth factors. Th
e growth factors we used were nerve growth factor (NGF), basic-fibrobl
ast growth factor (h-FGF), and glial cell-line derived neurotrophic fa
ctor (GDNF). In addition, we used glial conditioned medium derived fro
m either newborn mouse cerebral cortex (NBCC) or aged mouse cerebral h
emispheres (MACH), as a source of normal glial factors. Because these
cells express the cholinergic phenotype, we used choline acetyltransfe
rase (ChAT) activity as a biochemical marker for comparison. A differe
ntial responsiveness to these factors was observed between Neuro 2a an
d Neuro 2a-BM88. The presence of NGF, 25 ng/ml, in the culture medium
did not affect ChAT activity in either cell type. In contrast to NGF,
in the presence of b-FGF, 5 ng/ml, the transfected cells, Neuro 2a-BM8
8, responded with a marked increase in ChAT activity. On the other han
d, with GDNF, 1 ng/ml, only Neuro 2a cells showed an increase in ChAT
activity. Finally, we found no response to the glial conditioned media
, although these media contain several growth factors, including b-FGF
: In conclusion our findings show that overexpression of the neuron-sp
ecific antigen BM88 in neuroblastoma cells modifies their properties w
ith respect to growth factor sensitivity, and, hence, the Neuro 2a and
Neuro 2a-BM88 are suitable cell models to examine the role of growth
factors in neuronal differentiation. (C) 1998 Wiley-Liss, Inc.