Induction of apoptosis by p75 neurotrophin receptor in human neuroblastoma cells

The low-affinity nerve growth factor receptor p75(NTR) belongs to a membrane receptor superfamily whose members, in certain cell types, are able to transduce an apoptotic signal. To investigate the effect of p75(NTR) expression in neuroblastoma cells, we transfected the p75(NTR) CDNA into SK-N-BE cells, a neuroblastoma cell line that lacks expression of both p75(NTR) and TrkA. Cell clones expressing elevated levels of p75(NTR) showed a high degree of cell death by apoptosis, even in serum-supplemented medium. Moreover, the level of apoptosis correlated directly with the expression lever of the receptor, indicating that p75(NTR) could activate the cell death program by itself. Clones expressing p75(NTR) showed a dramatic increase of cell death when switched into serum-free medium; these cultures rapidly extinguished. This apoptotic effect was greatly inhibited by NGF treatment. Our results support the hypothesis that p75(NTR), when it is not bound by NGF, may play a role in neuronal selection during embryonic development and suggest that neuroblastomas may arise from immature neuroblasts that escape programmed cell death. Therefore, the loss of p75(NTR) expression in developing neural crest cells might be a primary event in the genesis of neuroblastoma.