| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 148, 1381-1385, Copyright © 1996 by American Society for Investigative Pathology
REGULAR ARTICLES |
SC Goldman, CY Chen, TJ Lansing, TM Gilmer and MB Kastan
Johns Hopkins Oncology Center, Baltimore, Maryland, USA.
Mutations of the p53 tumor suppressor gene are rarely found in neuroblastoma. Though typically a nuclear protein, a number of tumor cell types have recently been reported to exhibit cytoplasmic p53 immunostaining, and it has been suggested that altered cellular localization is another mechanism of inhibiting p53 function. We examined p53 protein expression, localization, and function in neuroblastoma cell lines with wild-type p53 genes. Basal p53 levels were largely confined to the cytoplasmic compartment in these cells. However, after irradiation, p53 protein levels increased predominately in the nucleus. Transcriptional activity of p53 was intact in these cells because "downstream" proteins, p21WAF1 and MDM2, were induced by irradiation. In contrast to a neuroblastoma cell line harboring a mutant p53 gene, the neuroblastoma cells with wild-type protein were associated with an intact G1 arrest after DNA damage. The induced nuclear protein in these neuroblastoma cells also appeared functional as measured by its capacity to bind to a DNA oligomer containing a p53- consensus sequence. We have concluded that although p53 expression in neuroblastoma cells is primarily localized to the cytosol, ionizing radiation induces a functional p53 protein in the nucleus and that this cytoplasmic sequestration of p53 in human neuroblastoma is not a mechanism of inactivating p53 function.
This article has been cited by other articles:
 |
|
 |
|
  D.-L. T. Koomoa, T. Borsics, D. J. Feith, C. C. Coleman, C. J. Wallick, I. Gamper, A. E. Pegg, and A. S. Bachmann Inhibition of S-adenosylmethionine decarboxylase by inhibitor SAM486A connects polyamine metabolism with p53-Mdm2-Akt/protein kinase B regulation and apoptosis in neuroblastoma Mol. Cancer Ther., July 1, 2009; 8(7): 2067 - 2075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Cattelani, R. Defferrari, S. Marsilio, R. Bussolari, O. Candini, F. Corradini, G. Ferrari-Amorotti, C. Guerzoni, L. Pecorari, C. Menin, et al. Impact of a Single Nucleotide Polymorphism in the MDM2 Gene on Neuroblastoma Development and Aggressiveness: Results of a Pilot Study on 239 Patients Clin. Cancer Res., June 1, 2008; 14(11): 3248 - 3253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Barbieri, P. Mehta, Z. Chen, L. Zhang, A. Slack, S. Berg, and J. M. Shohet MDM2 inhibition sensitizes neuroblastoma to chemotherapy-induced apoptotic cell death. Mol. Cancer Ther., September 1, 2006; 5(9): 2358 - 2365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Carr, E. Bell, A. D.J. Pearson, U. R. Kees, H. Beris, J. Lunec, and D. A. Tweddle Increased Frequency of Aberrations in the p53/MDM2/p14ARF Pathway in Neuroblastoma Cell Lines Established at Relapse Cancer Res., February 15, 2006; 66(4): 2138 - 2145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Cui, T. Li, and H.-F. Ding Linking of N-Myc to Death Receptor Machinery in Neuroblastoma Cells J. Biol. Chem., March 11, 2005; 280(10): 9474 - 9481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. P. McKenzie, M. K. Danks, R. W. Kriwacki, and L. C. Harris p21Waf1/Cip1 Dysfunction in Neuroblastoma: A Novel Mechanism of Attenuating G0-G1 Cell Cycle Arrest Cancer Res., July 1, 2003; 63(13): 3840 - 3844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Sembritzki, C. Hagel, K. Lamszus, W. Deppert, and W. Bohn Cytoplasmic localization of wild-type p53 in glioblastomas correlates with expression of vimentin and glial fibrillary acidic protein Neuro-oncol, July 1, 2002; 4(3): 171 - 178. [Abstract] [PDF]
|
|
|
|
|
|
H. Cui, A. Schroering, and H.-F. Ding p53 Mediates DNA Damaging Drug-induced Apoptosis through a Caspase-9-dependent Pathway in SH-SY5Y Neuroblastoma Cells Mol. Cancer Ther., July 1, 2002; 1(9): 679 - 686. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Wartiovaara, F. Barnabe-Heider, F. D. Miller, and D. R. Kaplan N-myc Promotes Survival and Induces S-Phase Entry of Postmitotic Sympathetic Neurons J. Neurosci., February 1, 2002; 22(3): 815 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Keshelava, J. J. Zuo, P. Chen, S. N. Waidyaratne, M. C. Luna, C. J. Gomer, T. J. Triche, and C. P. Reynolds Loss of p53 Function Confers High-Level Multidrug Resistance in Neuroblastoma Cell Lines Cancer Res., August 1, 2001; 61(16): 6185 - 6193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Tweddle, A. J. Malcolm, M. Cole, A. D.J. Pearson, and J. Lunec p53 Cellular Localization and Function in Neuroblastoma : Evidence for Defective G1 Arrest Despite WAF1 Induction in MYCN-Amplified Cells Am. J. Pathol., June 1, 2001; 158(6): 2067 - 2077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Fan, J. Iyer, S. Zhu, K. K. Frick, R. K. Wada, A. E. Eskenazi, P. E. Berg, N. Ikegaki, R. H. Kennett, and C. N. Frantz Inhibition of N-myc Expression and Induction of Apoptosis by Iron Chelation in Human Neuroblastoma Cells Cancer Res., February 1, 2001; 61(3): 1073 - 1079. [Abstract] [Full Text]
|
|
|
|
|
|
D. A. Tweddle, A. J. Malcolm, N. Bown, A. D. J. Pearson, and J. Lunec Evidence for the Development of p53 Mutations after Cytotoxic Therapy in a Neuroblastoma Cell Line Cancer Res., January 1, 2001; 61(1): 8 - 13. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. V. Gaitonde, W. Qi, R. R. Falsey, N. Sidell, and J. D. Martinez Morphologic Conversion of a Neuroblastoma-derived Cell Line by E6-mediated p53 Degradation Cell Growth Differ., January 1, 2001; 12(1): 19 - 27. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. M. Rodriguez-Lopez, D. Xenaki, T. O. B. Eden, J. A. Hickman, and C. M. Chresta MDM2 Mediated Nuclear Exclusion of p53 Attenuates Etoposide-Induced Apoptosis in Neuroblastoma Cells Mol. Pharmacol., January 1, 2001; 59(1): 135 - 143. [Abstract] [Full Text]
|
|
|
|
|
|
P. P. McKenzie, S. M. Guichard, D. S. Middlemas, R. A. Ashmun, M. K. Danks, and L. C. Harris Wild-Type p53 Can Induce p21 and Apoptosis in Neuroblastoma Cells But the DNA Damage-induced G1 Checkpoint Function Clin. Cancer Res., December 1, 1999; 5(12): 4199 - 4207. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Kirsch, A. Doseff, B. N. Chau, D.-S. Lim, N. C. de Souza-Pinto, R. Hansford, M. B. Kastan, Y. A. Lazebnik, and J. M. Hardwick Caspase-3-dependent Cleavage of Bcl-2 Promotes Release of Cytochrome c J. Biol. Chem., July 23, 1999; 274(30): 21155 - 21161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Maris and K. K. Matthay Molecular Biology of Neuroblastoma J. Clin. Oncol., July 1, 1999; 17(7): 2264 - 2264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Flagstad, P. A. Andresen, J. I. Johnsen, S. K. Asomani, G.-E. Jorgensen, S. Vignarajan, A. Kjuul, P. Kogner, and T. Traavik A Possible Contributory Role of BK Virus Infection in Neuroblastoma Development Cancer Res., March 1, 1999; 59(5): 1160 - 1163. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sutcliffe, L. Fu, J. Abraham, H. Vaziri, and S. Benchimol A Functional Wild-Type p53 Gene Is Expressed in Human Acute Myeloid Leukemia Cell Lines Blood, October 15, 1998; 92(8): 2977 - 2979. [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Giaccia and M. B. Kastan The complexity of p53 modulation: emerging patterns from divergent signals Genes & Dev., October 1, 1998; 12(19): 2973 - 2983. [Full Text]
|
|
|
|
 |
|
 A. G. Ostermeyer, E. Runko, B. Winkfield, B. Ahn, and U. M. Moll Cytoplasmically sequestered wild-type p53 protein in neuroblastoma is relocated to the nucleus by a C-terminal peptide PNAS, December 24, 1996; 93(26): 15190 - 15194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Isaacs, S.'i. Saito, and L. M. Neckers Requirement for HDM2 Activity in the Rapid Degradation of p53 in Neuroblastoma J. Biol. Chem., May 18, 2001; 276(21): 18497 - 18506. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
