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.
UNC-Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599, USA.
J S
JS
Isaacs
R
R
Hardman
T A
TA
Carman
J C
JC
Barrett
B E
BE
Weissman
D002460:Cell Line; D003593:Cytoplasm / Q000502:physiology; D016193:G1 Phase / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2 / Q000502:physiology; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D013347:Subcellular Fractions; D019098:Telomerase / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D019098:Telomerase