This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Douc-Rasy, S. Articles by Bénard, J. Search for Related Content PubMed PubMed Citation Articles by Douc-Rasy, S. Articles by Bénard, J.

(American Journal of Pathology. 2002;160:631-639.)
© 2002 American Society for Investigative Pathology

Regular Articles

N-p73 Accumulates in Human Neuroblastic Tumors

Sétha Douc-Rasy^*, Michel Barrois^*, Maria Echeynne^*, Mourad Kaghad, Etienne Blanc^*, Gilda Raguenez^*, David Goldschneider^*, Marie-José Terrier-Lacombe, Olivier Hartmann, Ute Moll^¶, Daniel Caput and Jean Bénard^*

From the Centre National de Recherche Scientifique-Unité Mixte deRecherche 1598 et Département de Biologie Clinique,^*
the Département de Pathologie,
and theDépartement de Pédiatrie,
InstitutGustave Roussy, Villejuif, France; SanofiRecherche,
Labège, France; and theDepartment of Pathology,^¶
State University of NewYork at Stony Brook, New York

Neuroblastic tumors (NTs), occurring in early childhood, display a wide spectrum of differentiation. Recurrent deletions involving the p73 locus are frequently observed in undifferentiated NTs. To address the question of the possible implication of p73 in neuroblastic differentiation, we investigated the status of the expression of this gene in a panel of differentiated and undifferentiated tumors. Although mutations were not found, p73 transcript profiles differed between undifferentiated and differentiated tumors. The frequency of the transcripts lacking exon 2 (species 1–3) appeared to be higher in undifferentiated than in differentiating and differentiated NTs. In contrast, products from using an alternate promoter (N-p73) were present in all NTs. In addition, only N-p73, but not full-length proteins, were detected by immunoblotting, suggesting a greater stability of N-truncated isoforms. Importantly, as in the adrenal medulla, most NTs showed p73-positive immunohistological staining with a cellular distribution and intensity varying according to the neuronal differentiation. Surprisingly, we observed redistribution of p73 from the nucleus to the cytoplasm during neuroblastic differentiation. Our data suggest that, in undifferentiated NTs, a link may exist between the accumulation of N-p73 variants and the "nuclear exclusion" of p53.

This article has been cited by other articles:

				E. Horvilleur, M. Bauer, D. Goldschneider, X. Mergui, A. de La Motte, J. Benard, S. Douc-Rasy, and D. Cappellen p73{alpha} isoforms drive opposite transcriptional and post-transcriptional regulation of MYCN expression in neuroblastoma cells Nucleic Acids Res., August 1, 2008; 36(13): 4222 - 4232. [Abstract] [Full Text] [PDF]

				A. Tannapfel, K. John, N. Mise, A. Schmidt, S. Buhlmann, S. M. Ibrahim, and B. M. Putzer Autonomous growth and hepatocarcinogenesis in transgenic mice expressing the p53 family inhibitor DNp73 Carcinogenesis, January 1, 2008; 29(1): 211 - 218. [Abstract] [Full Text] [PDF]

				H. Li, L. Yao, T. Ouyang, J. Li, T. Wang, Z. Fan, T. Fan, B. Dong, B. Lin, J. Li, et al. Association of p73 G4C14-to-A4T14 (GC/AT) polymorphism with breast cancer survival Carcinogenesis, February 1, 2007; 28(2): 372 - 377. [Abstract] [Full Text] [PDF]

				I. R. Watson, A. Blanch, D. C. C. Lin, M. Ohh, and M. S. Irwin Mdm2-mediated NEDD8 Modification of TAp73 Regulates Its Transactivation Function J. Biol. Chem., November 10, 2006; 281(45): 34096 - 34103. [Abstract] [Full Text] [PDF]

				J. Terrasson, S. Allart, H. Martin, J. Lule, H. Haddada, D. Caput, and C. Davrinche p73-Dependent Apoptosis through Death Receptor: Impairment by Human Cytomegalovirus Infection Cancer Res., April 1, 2005; 65(7): 2787 - 2794. [Abstract] [Full Text] [PDF]

				D. Goldschneider, K. Million, A. Meiller, H. Haddada, A. Puisieux, J. Benard, E. May, and S. Douc-Rasy The neurogene BTG2TIS21/PC3 is transactivated by {Delta}Np73{alpha} via p53 specifically in neuroblastoma cells J. Cell Sci., March 15, 2005; 118(6): 1245 - 1253. [Abstract] [Full Text] [PDF]

				H. Uramoto, K. Sugio, T. Oyama, S. Nakata, K. Ono, M. Morita, K. Funa, and K. Yasumoto Expression of {Delta}Np73 Predicts Poor Prognosis in Lung Cancer Clin. Cancer Res., October 15, 2004; 10(20): 6905 - 6911. [Abstract] [Full Text] [PDF]

				U. M. Moll and N. Slade p63 and p73: Roles in Development and Tumor Formation Mol. Cancer Res., July 1, 2004; 2(7): 371 - 386. [Abstract] [Full Text] [PDF]

				A. Santos, L. Calvet, M.-J. Terrier-Lacombe, A. Larsen, J. Benard, C. Pondarre, G. Aubert, J. Morizet, F. Lavelle, and G. Vassal In Vivo Treatment with CPT-11 Leads to Differentiation of Neuroblastoma Xenografts and Topoisomerase I Alterations Cancer Res., May 1, 2004; 64(9): 3223 - 3229. [Abstract] [Full Text] [PDF]

				D. Goldschneider, E. Blanc, G. Raguenez, M. Barrois, A. Legrand, G. Le Roux, H. Haddada, J. Benard, and S. Douc-Rasy Differential response of p53 target genes to p73 overexpression in SH-SY5Y neuroblastoma cell line J. Cell Sci., January 15, 2004; 117(2): 293 - 301. [Abstract] [Full Text] [PDF]

				T. Stiewe, S. Tuve, M. Peter, A. Tannapfel, A. H. Elmaagacli, and B. M. Putzer Quantitative TP73 Transcript Analysis in Hepatocellular Carcinomas Clin. Cancer Res., January 15, 2004; 10(2): 626 - 633. [Abstract] [Full Text] [PDF]

				P. Puig, P. Capodieci, M. Drobnjak, D. Verbel, C. Prives, C. Cordon-Cardo, and C. J. Di Como p73 Expression in Human Normal and Tumor Tissues: Loss of p73{alpha} Expression Is Associated with Tumor Progression in Bladder Cancer Clin. Cancer Res., November 15, 2003; 9(15): 5642 - 5651. [Abstract] [Full Text] [PDF]

				V. Vella, J. Zhu, F. Frasca, C.-Y. Li, P. Vigneri, R. Vigneri, and J. Y. J. Wang Exclusion of c-Abl from the Nucleus Restrains the p73 Tumor Suppression Function J. Biol. Chem., June 27, 2003; 278(27): 25151 - 25157. [Abstract] [Full Text] [PDF]