Corral M, Defer N, Paris B, Raymondjean M, Corcos D, Tichonicky L, Kruh J, Glaise D, Kneip B, Guguen-Guillouzo C
Cancer Res. 1986 Oct;46(10):5119-24.
In order to characterize the genes overexpressed in an hepatoma cell line, the HTC cells, and in diethylnitrosamine induced solid hepatomas, we constructed a complementary DNA library from HTC cells and performed differential screening with probes from HTC cells, from malignant nodules obtained 70 weeks after the carcinogen treatment, and from hepatocytes from normal rat liver. Eight clones corresponding to messenger RNAs (mRNAs) much more expressed in hepatomas than in hepatocytes from normal liver were isolated. Three, clones pHT 71, pHT 13, and pHT 26, were further analyzed by the study of their corresponding transcripts in hepatocytes from regenerating liver and in the hepatocytes from the nontumorous parts of the liver. Clone pHT 71 corresponds to a single 2.3-kilobase mRNA which is present in high levels in carcinoma nodules in hepatoma cell lines, in the nontumorous parts of the liver, and in hepatocytes isolated from regenerating liver 30 h after partial hepatectomy. Clone pHT 13 hybridizes with three distinct transcripts 3.8, 2.6, and 1.6 kilobases long. High levels of the 3.8- and 1.6-kilobase mRNAs are present in carcinoma nodules, in hepatoma cell lines, and in the nontumorous parts of the liver. However, the levels of these RNAs are similar in hepatocytes from regenerating liver and in hepatocytes obtained from normal rat liver. Clone pHT 26 corresponds to a 0.6-kilobase mRNA which exists at a high level only in cancer nodules and in hepatoma cell lines. We were unable to observe any cross-hybridization between these clones and the oncogenes which have been found to be expressed in hepatomas (c-fos, c-Ha-ras, c-Ki-ras, N-ras, and c-myc). The mRNAs corresponding to the three clones have not been detected in various tissues from normal adult rats. Our study shows that a high level of these mRNAs might be associated with rat liver carcinogenesis.
为了鉴定在肝癌细胞系HTC细胞以及二乙基亚硝胺诱导的实体肝癌中过表达的基因，我们构建了HTC细胞的互补DNA文库，并用来自HTC细胞、致癌物处理70周后获得的恶性结节以及正常大鼠肝脏肝细胞的探针进行差异筛选。分离出了8个与在肝癌中比正常肝脏肝细胞中表达得多得多的信使核糖核酸（mRNA）相对应的克隆。通过研究它们在再生肝肝细胞和肝脏非肿瘤部分的肝细胞中的相应转录本，对3个克隆pHT 71、pHT 13和pHT 26进行了进一步分析。克隆pHT 71对应于一个单一的2.3千碱基mRNA，其在肝癌细胞系的癌结节、肝脏的非肿瘤部分以及部分肝切除30小时后从再生肝分离的肝细胞中高水平存在。克隆pHT 13与3个分别为3.8、2.6和1.6千碱基长的不同转录本杂交。3.8千碱基和1.6千碱基mRNA在癌结节、肝癌细胞系和肝脏的非肿瘤部分高水平存在。然而，这些RNA在再生肝肝细胞和正常大鼠肝脏获得的肝细胞中的水平相似。克隆pHT 26对应于一个0.6千碱基mRNA，其仅在癌结节和肝癌细胞系中高水平存在。我们未能观察到这些克隆与已发现的在肝癌中表达的癌基因（c-fos、c-Ha-ras、c-Ki-ras、N-ras和c-myc）之间有任何交叉杂交。在正常成年大鼠的各种组织中未检测到与这3个克隆相对应的mRNA。我们的研究表明，这些mRNA的高水平可能与大鼠肝癌发生有关。
