Involvement of N-terminally truncated variants of p73, deltaTAp73, in head and neck squamous cell cancer: a comparison with p53 mutations.
p73, a p53-related gene, encodes two classes of isoforms with opposing functions: (1) a full-length transactivation-competent p73 protein (TAp73) with tumour suppressor activity; and (2) a group of NH2-terminally truncated, transactivation-deficient p73 proteins, deltaEx2p73, deltaEx2-3p73, deltaNp73 and deltaN'p73 (collectively named deltaTAp73) with oncogenic activity. In this study, for the first time, we analyse the deregulations of TAp73 and deltaTAp73 in head and neck squamous cell cancer (HNSCC) and compare them to p53 status. We found that all the p73 isoforms in HNSCC tissue were upregulated with respect to those in normal adjacent tissue. Concomitant upregulations of p73 transcripts were often found in cancer tissue but not in normal tissue. p53 mutations and p73 transcript alterations are not mutually exclusive. All the HNSCC specimens studied had at least one p53 mutation and/or one deltaTAp73 transcript alteration. Although both the deltaNp73 and the TAp73 transcripts were found to be upregulated in head and neck cancers, the predominant protein in the cancers analysed was deltaNp73. TAp73, in contrast, was only weakly expressed. This finding is highly relevant and sheds light on the puzzling question of the biological significance of TAp73 upregulation in cancers. deltaNp73 protein levels were significantly overexpressed in HNSCC tissue compared to matched normal tissue (p = 0.003). Furthermore, a trend was found for better overall survival in patients with a low expression of deltaNp73. Our results show that the deregulation of both the p53 and the p73 pathways plays an important role in inducing head and neck cancers.
Faridoni-Laurens
Laetitia
L
UPRESS 3535-IFR54 Univ Paris Sud, Institut Gustave Roussy, Villejuif, France.
Tourpin
Sophie
S
Alsafadi
Samar
S
Barrois
Michel
M
Temam
Stephane
S
Janot
François
F
Koscielny
Serge
S
Bosq
Jacques
J
Bénard
Jean
J
Ahomadegbe
Jean-Charles
JC
D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D040461:Gene Components; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics; D018307:Neoplasms, Squamous Cell / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human