Cell Growth & Differentiation, Vol 8, Issue 8 861-869, Copyright © 1997 by American Association of Cancer Research
Characterization of platelet-derived growth factor (PDGF) action on a mouse neuroblastoma cell line, NB41, by introduction of an antisense PDGF beta-receptor RNA
K Funa and A Ahgren
Ludwig Institute for Cancer Research, Biomedical Center, Uppsala, Sweden.
We have shown previously that platelet-derived growth factor (PDGF) has
trophic effects on dopaminergic neurons in vitro. We now examined a mouse
neuroblastoma cell line, NB41, for its response to PDGF and studied their
phenotypic characteristics following introduction of an antisense PDGF
beta-receptor RNA. NB41 cells produce both PDGF-AA and -BB; however, they
carry only PDGF beta-receptors, responding to BB but not to AA. Culturing
the cells with PDGF-BB induced mRNA for c-fos and PDGF-beta receptor as
well as that of neuron-specific enzyme, tyrosine hydroxylase. In contrast,
mRNA of chromogranin A, which is produced by chromaffin cells, decreased.
Introduction of an antisense PDGF beta-receptor RNA in NB41 cells
completely suppressed neurite extension and cell growth. We compared the
PDGF-beta receptor sense and antisense clones for their survival. Following
serum withdrawal, NB41 cells showed a DNA ladder, which by an addition of
the neurotoxin, 6-hydroxy dopamine (6-OHDA), resulted in a further
enhancement of the DNA ladder. The addition of PDGF-BB prior to 6-OHDA
rescued cells from undergoing apoptosis, seen as a reduction of the DNA
ladder. The antisense clone, regardless of the presence of PDGF-BB in the
culture, showed a pronounced DNA ladder after serum withdrawal, which was
further enhanced by the addition of 6-OHDA.