Reduced expression of p33(ING1) and the relationship with p53 expression in human gastric cancer.
p33(ING1) is a novel growth inhibitor candidate for a tumor suppressor gene. p33(ING1) cooperates with p53 and negatively regulates cell growth by activating transcription from the p21/WAF1 promoter even though it has no significant sequence similarity to p53. We first compared p33(ING1) expression in human gastric cancers and matched normal tissues using quantitative RT-PCR and real time 'Taqman TM' technology. A significant decrease in p33(ING1) expression was evident in 15 of 20 gastric cancers. In immunohistochemical analysis, p53 protein expression was detected in 4 of 20 (20%) tumors, and 12 of 15 (80%) tumors with decreasing p33(ING1) expression in RT-PCR had the wild type p53. When we examined the sequence of p33(ING1) in 12 gastrointestinal carcinoma cell lines, we found mutation in only one cell line, HCT116. Our findings are interpreted to mean that p33(ING1) may function as a tumor suppressor in gastric carcinogenesis, even though the gene is preserved in the majority of gastrointestinal carcinomas. It should be noted that expression of p33 decreased in many cancer patients, and the biological effects of p33(ING1) and p53 are interrelated and require the activity of both genes.
Oki
E
E
Cancer Center, Kyushu University Hospital, Fukuoka, Japan.
Maehara
Y
Y
Tokunaga
E
E
Kakeji
Y
Y
Sugimachi
K
K
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001706:Biopsy; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005456:Fluorescent Dyes; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D005456:Fluorescent Dyes; C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases