Transcriptional dysregulation of the p73L / p63 / p51 / p40 / KET gene in human squamous cell carcinomas: expression of Δ Np73L, a novel dominant-negative isoform, and loss of expression of the potential tumour suppressor p51

• DOI: 10.1054/bjoc.2000.1735
• Publication Date: 2002-07-26T07:31:53Z
• Authors: M Senoo; I Tsuchiya; Y Matsumura; T Mori; Y Saito; H Kato; T Okamoto; S Habu
• Keywords: 0301 basic medicine; Skin Neoplasms; Transcription, Genetic; Tumor Suppressor Proteins; Membrane Proteins; NADPH Oxidases; Nuclear Proteins; Proteins; Regular Article; Tumor Protein p73; Phosphoproteins; Cell Line; 3. Good health; DNA-Binding Proteins; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Carcinoma, Squamous Cell; Trans-Activators; Humans; Genes, Tumor Suppressor; Tumor Suppressor Protein p53; Transcription Factors

We have recently identified a second p53 -related p73L gene, also referred to as p63 / p51 p40 KET which encodes the 2 major isoforms and resulting from different exon usage at their amino terminal regions. Although are suspected play oncogenic tumour suppressive roles in mammalian cells, respectively, no evidence of linkage between expression these human cancers has been reported so far. In this study, we first investigated profile various cell lines found that novel isoform, termed DeltaNp73L, was predominantly expressed squamous carcinomas. The DeltaNp73L/p73L/p51 primary skin cancer specimens showed frequently lost (62%) but detected all normal samples. p51-expressing cancers, DeltaNp73L associated high frequency (75%) though it not tissues. Transient co-transfection data indicate possibility can inhibit p53-, more preferentially, p51-mediated transactivation. These suggest loss and/or might contribute pathogenesis