WHV/myc转基因小鼠肝癌发生过程中的基因异常

Abnormal expression of several oncogenes during hepatocarcinogenesis in WHV/myc transgeaic mice

目的探测ＷＨＶ／ｍｙｃ转基因小鼠肝癌发生过程中有关基因在肝脏中的异常表达。方法用原位杂交方法检测ＷＨＶ／ｍｙｃ转基因小鼠肝肿瘤形成的不同阶段，ｃ－ｍｙｃ转染基因、胰岛素样生长因子Ⅱ（ＩＧＦ－Ⅱ）基因ｃ－ｊｕｎ、ｃ－ｆｏｓ和ｃ－Ｈ－ｒａｓ等基因的表达。结果ｃ－ｍｙｃ转染基因和ＩＧＦ－Ⅱ基因在转基因小鼠出生后早期的肝脏中异常表达，随后表达水平即降低至不能测出。上述两基因的表达在肝肿瘤形成期重新出现。ｃ－ｊｕｎ、ｃ－ｆｏｓ和ｃ－Ｈ－ｒａｓ基因在转基因小鼠肝癌发生前肝脏中的表达强度明显高于正常小鼠。结论ｃ－ｍｙｏｔ染基因和ＩＧＦ－Ⅱ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；在ｃ－ｍｙｃ转染基因表达的“沉默”期，一些癌基因在肝脏中的异常表达对日后肝脏肿瘤的形成可能也具有一定作用。

Obiective To explore at cellular level the abnormal expfedon of related oncogrnesduring hepatocarcinogrnesis in the WHV/myc transgenic mice. Methods With speCific molecular probes, insitu hybridization was uest to detect the expredon of c-myc transgene,IGF-Ⅱ gene as well as c-jun,c- fos, and c-H-ras oncogrnes in the liver sections from WHV/myc transgrnic mice in different stabs of thecarcinogrnic process. Results The overexpressions of c-myc transgune and IGF-II bine transcripts weredetected in liver sections from the earlier neonatal transgrnic mice. Then, the expression levels of thesetwo g6nes were rapidly decreased and undetectable. At the time of the liver tumor development, theexpreSSion of c-myc transgrne and IGF-II gene resumed. The c-jun, c-fos and c-H-ras genes expressedmore intensely in the livers from preneoplastic WHV/myc mice than from normal mice. Conclusion Theoverexpressions of c-myc transgrne and IGF-II gene in the earlier neonatal stabs and tumoral stags maybe of importance for the development and maintenance of a transformed phenotype. During theprenoplastic 'silent' period of c-myc transgrne expression in WHV/myc transgrnic mice, several oncogrnesare overexpressed in the livers.