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用N-亚硝基吗啉诱导大鼠产生的癌前和肿瘤性肝脏病变中转铁蛋白基因表达的改变

Altered transferrin gene expression in preneoplastic and neoplastic liver lesions induced in rats with N-nitrosomorpholine.

作者信息

Schiebel K, Stumpf H, Zerban H, Pekel E, Bannasch P

机构信息

Abteilung für Cytopathologie, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany.

出版信息

Virchows Arch B Cell Pathol Incl Mol Pathol. 1992;62(4):251-7. doi: 10.1007/BF02899689.

DOI:10.1007/BF02899689
PMID:1359698
Abstract

The expression of the gene for the iron transport protein transferrin was found to be altered in preneoplastic and neoplastic lesions induced in the rat liver by N-nitrosomorpholine. The total RNA of ten hepatocellular carcinomas (HCC) was investigated by Northern blot analysis using a cDNA-probe comprising 150 bp of the 3' region and compared with the total hepatic RNA in untreated rats. Seven hepatocellular carcinomas showed slight or pronounced reduction in transferrin expression. In situ hybridization of two additional hepatocellular carcinomas revealed marked reduction in the mRNA level for the transferrin gene compared with the surrounding tissue. In contrast, the majority of early preneoplastic lesions storing excess glycogen and tigroid cell foci expressed increased levels of transferrin mRNA. The loss of glycogen in mixed cell foci, which represent a later stage of hepatocarcinogenesis, was usually accompanied by a decrease in transferrin mRNA suggesting a close relationship between this change in gene expression and cellular dedifferentiation emerging during hepatocarcinogenesis.

摘要

研究发现,N-亚硝基吗啉诱导的大鼠肝脏癌前病变和肿瘤性病变中,铁转运蛋白转铁蛋白的基因表达发生了改变。使用包含3'区域150 bp的cDNA探针,通过Northern印迹分析对10个肝细胞癌(HCC)的总RNA进行了研究,并与未处理大鼠的肝脏总RNA进行了比较。7个肝细胞癌显示转铁蛋白表达略有或明显降低。另外两个肝细胞癌的原位杂交显示,与周围组织相比,转铁蛋白基因的mRNA水平显著降低。相反,大多数储存过量糖原的早期癌前病变和虎斑细胞灶表达的转铁蛋白mRNA水平升高。混合细胞灶中糖原的丢失代表肝癌发生的后期阶段,通常伴随着转铁蛋白mRNA的减少,这表明这种基因表达变化与肝癌发生过程中出现的细胞去分化密切相关。

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