Differential subcellular p53 localization and function in N- and S-type neuroblastoma cell lines.

Neuroblastoma (NB) cells in vitro are capable of bidirectional transdifferentiation, resulting in two distinct, yet reversible, phenotypes of neuroblastic (N-type) and nonneuronal (S-type) Schwann-like cells. Our previous studies suggested that the wild-type p53 protein is subject to differential regulation in a subset of neuronal cell types. To further test this hypothesis, we compared p53 function in three matched pairs of N- and S-type cell lines, each pair originating from an individual NB tumor. Our data show that although p53 remains cytoplasmically sequestered in a punctate pattern in N-type cells after DNA damage, the protein is diffusely distributed in the S-type cells and is additionally capable of translocating to the nucleus and mediating a biological response to this damage. Our data, therefore, suggest that the p53 protein may be differentially regulated by a neuronal cellular environment and that the sequestration of p53 in NB may be reversible.