RRC ID 39957
Author Senoo M, Tsuchiya I, Matsumura Y, Mori T, Saito Y, Kato H, Okamoto T, Habu S.
Title Transcriptional dysregulation of the p73L / p63 / p51 / p40 / KET gene in human squamous cell carcinomas: expression of Delta Np73L, a novel dominant-negative isoform, and loss of expression of the potential tumour suppressor p51.
Journal Br. J. Cancer
Abstract We have recently identified a second p53 -related p73L gene, also referred to as p63 / p51 / p40 / KET gene, which encodes the 2 major isoforms p73L and p51 resulting from different exon usage at their amino terminal regions. Although p73L and p51 are suspected to play oncogenic and tumour suppressive roles in mammalian cells, respectively, no evidence of linkage between the expression of these isoforms and human cancers has been reported so far. In this study, we first investigated the expression profile of p51 and p73L in various human tumour cell lines and found that a novel isoform, termed DeltaNp73L, was predominantly expressed in squamous cell carcinomas. The expression profile of DeltaNp73L/p73L/p51 in primary human skin cancer specimens showed that the expression of p51 was frequently lost (62%) but was detected in all normal skin samples. In p51-expressing skin cancers, DeltaNp73L expression was associated at a high frequency (75%) though it was not detected in normal skin tissues. Transient co-transfection data indicate the possibility that DeltaNp73L can inhibit p53-, and more preferentially, p51-mediated transactivation. These data suggest that the loss of expression of p51 and/or the expression of DeltaNp73L might contribute to the pathogenesis of human squamous cell carcinomas.
Volume 84(9)
Pages 1235-41
Published 2001-5-4
DOI 10.1054/bjoc.2000.1735
PII S000709200091735X
PMID 11336476
PMC PMC2363892
MeSH Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / physiopathology Cell Line DNA-Binding Proteins / biosynthesis* DNA-Binding Proteins / genetics Gene Expression Regulation, Neoplastic* Genes, Tumor Suppressor Humans Membrane Proteins* NADPH Oxidases Nuclear Proteins / biosynthesis* Nuclear Proteins / genetics Phosphoproteins / biosynthesis* Phosphoproteins / genetics Proteins* Skin Neoplasms / genetics* Skin Neoplasms / physiopathology Trans-Activators* Transcription Factors Transcription, Genetic Tumor Protein p73 Tumor Suppressor Protein p53 / biosynthesis* Tumor Suppressor Protein p53 / genetics Tumor Suppressor Proteins
IF 5.922
Times Cited 42
Human and Animal Cells