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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inducible genes and oxidative stress-inducible genes were identified in both the CH-C and HCC libraries, and some unpublished new genes were specifically up- or down-regulated in the HCC library.DNA micro array containing 1,080 genes covering various categories of genes including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.

通过SAGE（基因表达系列分析）方法分析正常肝脏、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总共 30,982 个序列标签，其中 8,596 个标签源自独特基因。正常肝脏中高表达的基因是编码血浆蛋白（>总转录本的21.8%）、细胞质蛋白（>8.6%）、酶（>4.8%）、蛋白酶抑制剂（>1.7%）、补体（>1.1!%）和凝血因子（>0.75%）的基因。大约 13.9% 的转录本编码迄今为止 GenBank 中未报道的基因。与CH-C和NL文库中的标签相比，HCC文库中的标签显示出许多差异表达基因的存在。 CH-C和HCC文库均发现IFN-γ诱导基因和氧化应激诱导基因上调，一些未发表的新基因在HCC文库中特异性上调或下调。DNA微阵列包含1,080个基因，涵盖癌基因、抑癌基因、凋亡相关基因、细胞周期相关基因等多种类别基因。开发的。基因表达谱的层次聚类分析表明，乙型和丙型肝炎病毒感染，而不是年龄、性别或肝炎组织学，是决定聚类的显着因素（P < 0.05）。在乙型肝炎组织病变中，与炎症相关的基因占主导地位，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。 HCC组织的基因表达谱分析表明，一些基因根据肿瘤分化具有特征性基因表达模式。