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Genomics of liver cells anォ liver cancer cells

肝细胞和肝癌细胞的基因组学

基本信息

批准号：
11307010
负责人：
KOBAYASHI Kenichi
金额：
$ 19.34万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Gene expression profile of normal liver, liver tissue from chronic hepatitis C (CH-C) and liver cancer (HCC) were analyzed by SAGE (serial analysis of gene expression) method. Total of 30,982 sequence tags were separated from normal tissue, in which 8,596 tags were derived from unique genes. The genes highly expressed in the normal liver were those encoding plasma proteins (>21.8% of total transcripts), cytoplasmic proteins (>8.6%), enzymes (>4.8%), protease inhibitors (>1.7%), complements (>1.1!%), and coagulation factors (>0.75%). About 13.9% of all transcripts encoded genes not reported in GenBank thus far. Tags from the HCC library exhibited the existence of many differentially expressed genes compared with those from the CH-C and NL libraries. Up-regulation of IFN-gamma inducible genes and oxidative stress-inducible genes were identified in both the CH-C and HCC libraries, and some unpublished new genes were specifically up- or down-regulated in the HCC library.DNA micro array containing 1,080 genes covering various categories of genes including oncogenes, tumor suppressor genes, apoptosis related genes, cell cycle related genes were originally developed. Hierarchical clustering analysis of the gene expression profiles showed that Hepatitis B and C virus infection, but not age, sex, or histology of hepatitis, were significant factors determining clustering (P 0.05). In hepatitis B tissue lesions, genes involved in inflammation were predominant, whereas in hepatitis C, expression of anti-inflammatory response genes was relatively dominant. In addition, clustering analysis of DNA micro array data showed that tumor marker alpha-fetoprotein producing hepatoma cell lines shares common expression profile of genes in various categories. Analysis of gene expression profile of HCC tissues showed that some genes had characteristic gene expression pattern according to tumor differentiation.

采用基因表达序列分析(SAGE)方法分析正常肝、慢性丙型肝炎(CH-C)和肝癌(HCC)肝组织的基因表达谱。从正常组织中分离出30982个序列标签，其中8596个标签来自独特的基因。在正常肝脏中高表达的基因包括编码血浆蛋白(占总转录本的21.8%)、胞浆蛋白(占8.6%)、酶(占4.8%)、蛋白酶抑制物(占1.7%)、补体(占1.1！%)和凝血因子(占0.75%)。到目前为止，约有13.9%的转录本编码了GenBank中未报道的基因。与来自CH-C和NL文库的标签相比，来自肝细胞癌文库的标签显示存在许多差异表达的基因。在CH-C和肝细胞癌文库中都发现了干扰素-γ诱导基因和氧化应激诱导基因的上调，一些未发表的新基因在肝细胞癌文库中有特异性的上调或下调。基因表达谱的等级聚类分析表明，决定基因聚集性的显著因素是乙型和丙型肝炎病毒感染，而不是年龄、性别或肝炎的组织学(P<0.05)。在乙肝组织病变中，炎症相关基因占主导地位，而在丙型肝炎中，抗炎反应基因的表达相对占优势。此外，DNA微阵列数据的聚类分析表明，产生肿瘤标志物甲胎蛋白的肝癌细胞系在不同类别中具有共同的基因表达谱。对肝细胞癌组织的基因表达谱分析表明，根据肿瘤分化程度不同，某些基因具有特征性的基因表达模式。