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WHV/myc转基因小鼠肝癌发生过程中c-myc基因表达的双相性

Biphasic expression of c-myc transgene during hepatocarcinogenesis in WHV/myc transgenic mice

  • 摘要: 目的:WHV/myc转基因小鼠其肝脏肿瘤的自然发生率很高,本研究旨在细胞水平探测WHV/myc转基因小鼠肝癌发生过程中。c-myc转染基因的表达方式和肝细胞的增殖活性。方法:用核酸分子原位杂交的方法,检测了WHV/myc转基因小鼠肝肿瘤形成的不同阶段肝组织中c-myc基因的表达,同时检测了细胞增殖标志-组蛋白H3-2mRNA的表达。结果:10天龄小鼠肝脏中c-myc转染基因呈中等程度的表达,伴随30%的肝细胞增殖。随后,该基因表达水平迅速降低,在2月龄、4月龄和9月龄小鼠的肝脏中均不能够检测出。此期间肝细胞的增殖活性亦处于低水平。c-myc转染基因的表达重新出现于肿瘤形成期,肝腺瘤和肝癌的表达方式和强度相仿。肝细胞的增殖活性在此期约为14%左右。结论:c-myc转染基因在小鼠出生后早期和肿瘤形成期的异常表达对肝肿瘤的发生和瘤细胞转化表型的维持可能具有重要意义。

     

    Abstract: WHV/myc transgenic mice develop liver tumors spontaneously at a high frequency. The aim of this study was to explore at cellular level the expression pattern of c-myc transgene and to examine the proliferation of liver cells during hepatocarcinogenesis in the mice. Methods:With a specific molecular probe, in situ hybridization was used to detect the expression of c-myc transgene in the liver tissue sections from WHV/myc transgenic mice at different stages of the carcinogenic process. The expression of histone H3-2 mRNA, as a marker of cell prolifer, ation, was also examined. Results :In 10 days-old transgenic mouse livers, c-myc transgene transcripts were detected at moderate level over all hepatocytes and 30% of liver cells expressed histone H3-2 mRNA. Then, the expression level of the gene decreased rapidly. In 2 months--old, 4months-old and 9 months-old transgenic mouse livers, no significant signal for c-myc transgene transcripts was detected and the proliferative activity of liver cells was weak.The expression of c--myc transgene resumed at the stage of tumor development. Hepatic adenomas and hepatocarcinomas expressed the gene in the same pattern and intensity,and about 14% of the tumoral cells were in proliferative state at this stage. Conclusion:These data suggest that the overexpression of c--myc transgene in the early post-natal period and at the tumoral stage might be of importance for the development and maintenance of a transformed phenotype.

     

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