Wild-type p53 can induce p21 and apoptosis in neuroblastoma cells but the DNA damage-induced G(1) checkpoint function is attenuated

p53 is a tumor suppressor protein important in the regulation of apoptosis, Because p53 functions as a transcription factor, cellular responses depend upon activity of p53 localized in the nucleus. Cytoplasmic sequestration o f p53 has been proposed as a mechanism by which the function of this protei n can be suppressed, particularly in tumor types such as neuroblastoma in w hich the frequency of mutations of p53 is low. Data presented here demonstr ate that nuclear p53 protein is expressed in a panel of neuroblastoma cell lines, and after exposure to DNA damage, transcriptionally active p53 expre ssion can be induced. After exposure to both equitoxic IC80 and 10-Gy doses of ionizing radiation, both p53 and p21 were induced, but G(1) cell cycle arrest was attenuated. To investigate whether the DNA damage signaling path way was incapable of inducing sufficient p53 in these cells, we expressed a dditional wild-type p53 after adenoviral vector transduction. This exogenou s p53 expression also resulted in p21 induction but was unable to enhance t he G(1) arrest, suggesting that the pathway downstream from p53 is nonfunct ional. Although p53-mediated G(1) arrest is attenuated in neuroblastoma cel ls, the ability of p53 to induce apoptosis appears functional, consistent,v ith its chemosensitive phenotype, This work demonstrates that p53 is expres sed in the nucleus of neuroblastoma cells and can mediate induction of p21. However, this cell type appears to have an attenuated ability to mediate a DNA damage-induced G(1) cell cycle arrest.