title: Genetic alterations of tumor suppressor ING1 in human non-small cell lung cancer.
abstract: The aim of this study was to investigate the function of the ING1 gene in lung carcinoma. To detect the inhibitory effect of ING1 in human lung cancer, recombinant ING1b plasmids were transfected into two lung cancer cell lines with different p53 status, A549 with wild-type p53 (wtp53) and SK-MES-1 with mutant p53. Apoptosis, cell cycle, growth rate and the expression of downstream gene p21waf1 were analyzed. In addition, the complex of p33ING1b and p53 was analyzed with coimmunoprecipitation. To detect the gene alteration and the expression of ING1, 70 cases of fresh-frozen lung carcinomas and 217 cases of formalin-fixed, paraffin-embedded specimens were examined for loss of heterozygosity (LOH) and p33ING1b protein expression by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) and immunohistochemistry using tissue microarrays, respectively. Overexpression of ING1b inhibited the cell growth of A549 and SK-MES-1, induced cell cycle arrest and apoptosis. p21waf1 was up-regulated and a complex of p33ING1b and wtp53 was found after transfection of ING1b in the wtp53-positive lung cancer cell. High LOH frequency was found in lung carcinomas (55.7%) and p33ING1b expression was lost in 115 of 217 carcinomas (53.0%). Furthermore, there was a highly significant inverse correlation between expression and LOH frequency (P<0.05). ING1 can inhibit the growth of lung cancer cell lines through the induction of cell cycle arrest and apoptosis by forming a complex with wtp53 and up-regulating p21waf1. In human lung cancer, expression of the ING1 gene was reduced or lost and high LOH frequency of ING1 microsatellites was found. The LOH of microsatellites may down-regulate p33ING1b and/or affect its function, thereby, contributing to lung cell carcinogenesis.
authors.affiliation: Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Luo
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhu
authors.forename: Can-Rong
authors.initials: CR
authors.lastname: Ni
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Zhu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D049109:Cell Proliferation; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C501503:ING1 protein, human; D000076023:Inhibitor of Growth Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins