Fiche publication
Date publication
septembre 2008
Journal
The European respiratory journal
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MASCAUX Céline
Tous les auteurs :
Mascaux C, Bex F, Martin B, Burny A, Haller A, Paesmans M, Willard-Gallo K, Ninane V, Sculier JP
Lien Pubmed
Résumé
Murine double minute clone 2 (MDM2), p14 alternate reading frame (p14arf), and nucleophosmin (NPM) regulate p53 activity. A total of 200 biopsies, including normal bronchial, pre-invasive and invasive tissues, were examined for changes in NPM, p14arf, MDM2 and p53 expression patterns by immunohistochemistry and immunofluorescence with confocal microscopy. NPM and p14arf displayed a diffuse nuclear staining in most normal bronchial tissue. The fraction of biopsies displaying an increased MDM2 staining or a nucleolar relocalisation of NPM increased at mild and moderate dysplasia, respectively. Two different modifications occurred in p14arf expression, i.e. its loss or its nucleolar relocalisation, both increasing at severe dysplasia and both being associated with high MDM2 expression. In addition, the nucleolar relocalisation of p14arf was associated with that of NPM. Immunofluorescence staining indicated that NPM and p14arf either co-localised in the nucleoplasm or in the nucleoli, before and as a result of severe dysplasia, respectively. MDM2 was not detected in the nucleoli. Thus, changes occur in murine double minute clone 2, p14 alternate reading frame and nucleophosmin level of expression and/or cellular distribution during early steps of lung carcinogenesis. Their relative localisation as determined by immunofluorescence, supports the hypothesis that p14 alternate reading frame nucleolar relocalisation impairs p14 alternate reading frame-murine double minute clone 2 complex formation and that nucleophosmin might sequester p14 alternate reading frame. The demonstration of this hypothesis requires further functional studies.
Mots clés
Bronchial Neoplasms, metabolism, Carcinoma, Squamous Cell, metabolism, Case-Control Studies, Cell Nucleolus, metabolism, Humans, Nuclear Proteins, metabolism, Proto-Oncogene Proteins c-mdm2, metabolism, Tumor Suppressor Protein p14ARF, metabolism
Référence
Eur. Respir. J.. 2008 Sep;32(3):678-86
