Elevated and biallelic expression of p73 is associated with progression ofhuman bladder cancer

p73, a member of the p53 family at 1p36.3, has been demonstrated to be expr essed monoallelically and induce apoptosis or G(1) arrest of the cell cycle , To explore the candidacy of p73 as a suppressor in bladder tumorigenesis, we examined expression level, allelic origin, and mutation of p73 mRNA in 45 primary bladder carcinomas. Quantitative PCR analysis showed no allelic loss of the gene but showed various levels of mRNA expression in both carci noma and noncancerous tissues. Elevated expression of p73 was frequently ob served in carcinoma tissues [18 (40.0 %) of 45] and showed a strong correla tion with tumor stage or grade. Allotyping analysis using a StyI polymorphi sm detected biallelic expression in 12 (52.2%) of 23 heterozygous carcinoma s but none in 4 noncancerous tissues. Tumor-specific biallelic expression w as also identified from one matched set. In addition, 8 (66.7%) of these 12 expressed high levels of p73 mRNA, whereas only 2 (18.2%) of 11 monoalleli c expressors showed high expression, which suggests that the increased expr ession of p73 might be caused by the transcriptional activation of a silent allele in carcinomas. Single-strand conformational polymorphism analysis o f the entire coding region of p73 revealed no mutation, whereas 12 (26.7%) of the same set showed p53 alterations, No relationship between expression of p73 and p53 mutation or expression of p21(Waf1) or MDM2 was identified. Taken together, our data argue that p73 does not play a role as a tumor sup pressor in bladder carcinogenesis and suggest that the activation of a sile nt allele may contribute to the progression of bladder tumors.