Overexpression of the wild type p73 gene in human bladder cancer.
p73, a first p53 relative, was recently identified and shown to be monoallelically expressed in a number of different human tissues. To determine the potential role of this gene in human bladder cancer, we investigated p73 expression levels, allelic expression patterns, and analysed p73 mutations in 23 unselected primary invasive bladder cancers with matched normal tissues and in seven bladder cancer cell lines. In a comparison between normal and tumor tissues using quantitative RT-PCR analysis, we found that p73 was overexpressed in 22/23 bladder cancers, sometimes as great as 20-fold. Allelic expression analysis using a C/T polymorphism in exon 2 and a newly identified T/C polymorphism in exon 5 revealed that p73 was biallelically expressed in both normal bladder and cancer tissues, suggesting that p73 is not imprinted in bladder tissue. Mutation screening of the p73 gene in bladder cancer DNAs using denaturing high-performance liquid chromatography analysis and DNA sequencing revealed no tumor-specific mutations in any coding exons of the p73 gene. These data suggest that the p73 is unlikely to be a tumor suppressor gene, but that overexpression of p73 may contribute to tumorigenesis in bladder cancer.
Yokomizo
A
A
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55095, USA.
Mai
M
M
Tindall
D J
DJ
Cheng
L
L
Bostwick
D G
DG
Naito
S
S
Smith
D I
DI
Liu
W
W
D000483:Alleles; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins