HEPATITIS-B VIRUS-DNA INTEGRATION IN A SEQUENCE HOMOLOGOUS TO V-ERB-A AND STEROID-RECEPTOR GENES IN A HEPATOCELLULAR-CARCINOMA

HEPATITIS-B VIRUS-DNA INTEGRATION IN A SEQUENCE HOMOLOGOUS TO V-ERB-A AND STEROID-RECEPTOR GENES IN A HEPATOCELLULAR-CARCINOMA
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DOI:
10.1038/322070a0
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发表时间:
1986-07-03
期刊:
影响因子:
64.8
通讯作者:
TIOLLAIS, P
TIOLLAIS, P
中科院分区:
综合性期刊1区
文献类型:
--
作者:
DEJEAN, A;BOUGUELERET, L;TIOLLAIS, P

文献摘要

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乙型肝炎病毒(HBV)显然参与了人类肝细胞癌(HCC)的病因学1,并且在几乎所有HCC研究中发现HBV DNA整合到人类肝脏DNA 2 - 7,这表明这些整合的病毒序列可能参与了肝脏肿瘤的发生。在分子克隆后分析了几种HBV在不同HCCs8、9和hccs10 - 14中的整合,但没有发现HBV的明显作用。通过比较特定hcc8中存在的HBV整合位点与同一肝脏非肿瘤组织中相应的未占用位点,我们现在报道HBV整合将病毒序列置于肝细胞序列旁边,该序列与致癌基因(v- erbb - a)以及人类糖皮质激素受体和人类雌激素受体基因的假定dna结合结构域具有惊人的相似性。我们认为,该基因通常在正常肝细胞中沉默或转录水平非常低,由于HBV整合而变得不适当表达,从而促进细胞转化。
Hepatitis B virus (HBV) is clearly involved in the aetiology of human hepatocellular carcinoma (HCC)1and the finding of HBV DNA integration into human liver DNA in almost all HCCs studied2–7suggested that these integrated viral sequences may be involved in liver oncogenesis. Several HBV integrations in different HCCs8,9and HCC-derived cell lines10–14have been analysed after molecular cloning without revealing any obvious role for HBV. From a comparison of a HBV integration site present in a particular HCC8with the corresponding unoccupied site in the non-tumorous tissue of the same liver, we now report that HBV integration places the viral sequence next to a liver cell sequence which bears a striking resemblance to both an oncogene (v-erb-A) and the supposed DNA-binding domain of the human glucocorticoid receptor and human oestrogen receptor genes. We suggest that this gene, usually silent or transcribed at a very low level in normal hepatocytes, becomes inappropriately expressed as a consequence of HBV integration, thus contributing to the cell transformation.