title: Loss of imprinting and elevated expression of wild-type p73 in human gastric adenocarcinoma.
abstract: The p73 gene located at 1p36.3 encodes for a protein with significant similarity to p53. To investigate the penetrance of p73 in gastric carcinogenesis, we analyzed the expression, allelotype, and mutation of p73 in five cell lines and 75 tissues. Although extremely low levels of p73 expression were 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 polymorphism revealed that 5 of 21 (23.8%) informative carcinomas, but none of 19 noncancerous cases, express p73 biallelically, suggesting the transcriptional activation of a silent allele in a subset of cancers. Whereas the transcription of an active allele was markedly induced by serum starvation or clump formation of the cells, treatment with 5-aza-2'deoxycytidine activated a silent allele with a subsequent up-regulation of an active allele, supporting the genomic imprinting and autoregulation of the gene. Allelic deletion or mutation of the gene was not found, and no association of p73 expression with the mutational status of p53 or expression of p21Waf1 was recognized. Taken together, this study argues that p73 is not a target of genetic alteration in gastric carcinogenesis and suggests that overexpression of p73 might be triggered by physiological stresses accompanied with outgrowth of tumors, such as hypoxia or nutrient deprivation.
authors.affiliation: Department of Pathology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea. sgchi@nms.kyunghee.ac.Kr
authors.forename: M J
authors.initials: MJ
authors.lastname: Kang
authors.forename: B J
authors.initials: BJ
authors.lastname: Park
authors.forename: D S
authors.initials: DS
authors.lastname: Byun
authors.forename: J I
authors.initials: JI
authors.lastname: Park
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: J H
authors.initials: JH
authors.lastname: Park
authors.forename: S G
authors.initials: SG
authors.lastname: Chi
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000483:Alleles; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor; D018392:Genomic Imprinting; D018922:HL-60 Cells; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D025521:Tumor Suppressor Proteins; D020298:U937 Cells
chemical_list: C493956:CDKN1A protein, human; D016895:Culture Media, Serum-Free; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D000077209:Decitabine; D001374:Azacitidine