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

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.