Loss of imprinting and elevated expression of wild-type p73 in human gastric adenocarcinoma

The p73 gene located at 1p36.3 encodes for a protein with significant simil arity to p.53. To investigate the penetrance of p73 in gastric carcinogenes is, we analyzed the expression, allelotype, and mutation of p73 in five cel l lines and 75 tissues. Although extremely low levels of p73 expression wer e observed in all noncancerous gastric tissues and four of five cell lines, a significant elevation of p73 was detected in 37 of 39 (94.9%) carcinoma tissues. Furthermore, a tumor-specific increase of p73 was identified in 14 of 16 (87.5%) matched sets. Allelotyping analysis using a StyI or BanI pol ymorphism revealed that 5 of 21 (23.8 %) informative carcinomas, but none o f 19 noncancerous cases, express p73 biallelically, suggesting the transcri ptional activation of a silent allele in a subset of cancers. Whereas the t ranscription of an active allele was markedly induced by serum starvation o r clump formation of the cells, treatment with 5-aza-2'deoxycytidine activa ted a silent allele with a subsequent up-regulation of an active allele, su pporting the genomic imprinting and autoregulation of the gene. Allelic del etion or mutation of the gene was not found, and no association of p73 expr ession with the mutational status of p53 or expression of p21(Waf1) was rec ognized. Taken together, this study argues that p73 is not a target of gene tic alteration in gastric carcinogenesis and suggests that overexpression o f p73 might be triggered by physiological stresses accompanied with outgrow th of tumors, such as hypoxia or nutrient deprivation.