The hepatitis B virus X gene potentiates c-myc-induced liver oncogenesis in transgenic mice
The hepatitis B virus X gene potentiates c-myc-induced liver oncogenesis in transgenic mice
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DOI：
10.1038/sj.onc.1200850
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发表时间：
1997-01-30
期刊：
影响因子：
8
通讯作者：
Buendia, MA
中科院分区：
文献类型：
--
作者：
Terradillos, O;Billet, O;Buendia, MA
乙型肝炎病毒 X 蛋白 (HBx) 被认为与肝细胞癌的发展有关，但其确切功能仍存在争议，来自 PEX7 和 AX16 谱系的转基因小鼠在不同病毒调节元件的控制下在肝脏中表达 HBx，不会出现肝脏病理学（Billet 等人，1995），我们已将这两个小鼠谱系与 WHV/c-myc 进行杂交。 土拨鼠肝炎病毒 (WHV) 调控序列驱动的 c-myc 肝脏特异性表达导致所有动物罹患肝癌，与简单的 c-myc 转基因同窝小鼠相比，所有群体的双转基因动物的平均肿瘤潜伏期缩短了 2 至 3 个月，在肿瘤前期，成年双转基因小鼠的 c-myc 表达增强了四到五倍 与简单的WHV/c-myc转基因相比，转基因增加了肝细胞增殖和更广泛的肝脏病变，因此在该模型中，单独的HBx没有直接的病理作用，但它被证明可以加速c-myc诱导的肿瘤发展。这里提供的数据牢固地确立了 HBx 的致癌潜力，显然充当肿瘤促进剂。该模型为研究 HBx 反式激活靶基因表达并解除体内肝细胞生长控制的机制提供了独特的机会。
The hepatitis B virus X protein (HBx) is thought to be implicated in the development of hepatocellular carcinoma, but its exact function remains controversial, Transgenic mice from PEX7 and AX16 lineages that express HBx in the liver under control of different viral regulatory elements develop no liver pathology (Billet ed al., 1995), We have crossed these two mouse lineages with WHV/c-myc oncomice in which liver-specific expression of c-myc driven by woodchuck hepatitis virus (WHV) regulatory sequences causes liver cancer in all animals, The average tumor latency was shortened by 2 to 3 months in bitransgenic animals from all populations compared with simple c-myc transgenic littermates, At preneoplastic stages, adult bitransgenic mice showed four to fivefold enhanced expression of the c-myc transgene, increased hepatocyte proliferation and more extensive liver lesions compared with simple WHV/c-myc transgenics, Thus in this model, HBx alone has no direct pathological effect but it is shown to accelerate tumor development induced by c-myc. The data presented here firmly establish the oncogenic potential of HBx, apparently acting as a tumor promoter, This model offers unique opportunities to investigate the mechanisms by which HBx trans-activates the expression of target genes and deregulates the hepatocyte growth control in vivo.