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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。
OBJECTIVE: The natural incidence of liver tumors in WHV/myc transgenic mice is very high. This study aimed to detect the progression of liver cancer in WHV/myc transgenic mice at the cellular level. The expression pattern of c-myc transfected genes and the proliferation activity of hepatocytes. METHODS: The expression of c-myc gene in hepatic tissue at different stages of liver tumor formation in WHV/myc transgenic mice was detected by in situ hybridization of nucleic acid molecules. The expression of histone H3-2 mRNA was also detected. RESULTS: The c-myc transfected gene was moderately expressed in the liver of 10-day-old mice, accompanied by 30% hepatocyte proliferation. Subsequently, the expression level of the gene rapidly decreased and could not be detected in the liver of 2-month-old, 4-month-old, and 9-month-old mice. During this period, the proliferation activity of hepatocytes was also low. The expression of c-myc transfected gene reappeared in the tumorigenesis phase, and the expression pattern and intensity of hepatic adenoma and liver cancer were similar. The proliferation activity of hepatocytes is approximately 14% during this period. Conclusion: The abnormal expression of c-myc transfected gene in the early stage of mouse birth and tumor formation may have important significance for the occurrence of hepatic tumor and the maintenance of tumor cell transformation phenotype.