title: Expression of C-terminal deleted p53 isoforms in neuroblastoma.
abstract: The tumor suppressor gene, p53, is rarely mutated in neuroblastomas (NB) at the time of diagnosis, but its dysfunction could result from a nonfunctional conformation or cytoplasmic sequestration of the wild-type p53 protein. However, p53 mutation, when it occurs, is found in NB tumors with drug resistance acquired over the course of chemotherapy. As yet, no study has been devoted to the function of the specific p53 mutants identified in NB cells. This study includes characterization and functional analysis of p53 expressed in eight cell lines: three wild-type cell lines and five cell lines harboring mutations. We identified two transcription-inactive p53 variants truncated in the C-terminus, one of which corresponded to the p53beta isoform recently identified in normal tissue by Bourdon et al. [J. C. Bourdon, K. Fernandes, F. Murray-Zmijewski, G. Liu, A. Diot, D. P. Xirodimas, M. K. Saville and D. P. Lane (2005) Genes Dev., 19, 2122-2137]. Our results show, for the first time, that the p53beta isoform is the only p53 species to be endogenously expressed in the human NB cell line SK-N-AS, suggesting that the C-terminus truncated p53 isoforms may play an important role in NB tumor development.
authors.affiliation: Centre National de Recherche Scientifique, UMR 8126, Institut Gustave Roussy, 94805 Villejuif, France.
authors.forename: David
authors.initials: D
authors.lastname: Goldschneider
authors.forename: Emilie
authors.initials: E
authors.lastname: Horvilleur
authors.forename: Louis-François
authors.initials: LF
authors.lastname: Plassa
authors.forename: Marine
authors.initials: M
authors.lastname: Guillaud-Bataille
authors.forename: Karine
authors.initials: K
authors.lastname: Million
authors.forename: Evelyne
authors.initials: E
authors.lastname: Wittmer-Dupret
authors.forename: Gisèle
authors.initials: G
authors.lastname: Danglot
authors.forename: Hughes
authors.initials: H
authors.lastname: de Thé
authors.forename: Jean
authors.initials: J
authors.lastname: Bénard
authors.forename: Evelyne
authors.initials: E
authors.lastname: May
authors.forename: Sétha
authors.initials: S
authors.lastname: Douc-Rasy
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D018628:Gene Dosage; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015003:Yeasts / Q000235:genetics
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D020033:Protein Isoforms; D016159:Tumor Suppressor Protein p53