Ml. Schmidt et al., THE BIOLOGICAL EFFECTS OF ANTISENSE N-MYC EXPRESSION IN HUMAN NEUROBLASTOMA, Cell growth & differentiation, 5(2), 1994, pp. 171-178
Although N-myc amplification and overexpression are believed to play a
n important role in determining the clinical behavior of neuroblastoma
(NB), the exact function of N-myc in NB cell growth and differentiati
on remains unknown. To better understand the function of N-myc, an est
ablished human NB cell line was transfected with N-myc antisense (AS)
complementary DNA in an effort to down-regulate N-myc gene expression.
Five clones expressing AS N-myc RNA have been maintained in culture f
or over 2 years. Compared to control cells, a 30-69% decrease in the q
uantity of N-myc protein was demonstrated by Western blot analysis in
4 of the 5 AS clones. All 5 of the AS clones exhibited a 50-75% decrea
se in colony formation in soft agar assays compared to control cells.
In addition, all 5 AS clones expressed a 3.2-kilobase protein kinase C
-alpha transcript, whereas this message was not detected by Northern b
lot analysis in any of the control clones. These results suggest that
N-myc may play an important role in NB cell growth and that antisense
N-myc expression is associated with an induction of protein kinase C-a
lpha RNA expression. Further characterization of the AS clones may pro
vide insight into the function of N-myc and may thus lead to a better
understanding of the role that N-myc plays in determining the clinical
behavior of this childhood neoplasm.