Two genes associated with liver cancer are regulated by different mechanisms in rasT24 transformed liver epithelial cells.

We compared the regulation of gamma-glutamyl transferase (gamma GT) and glutathione-S-transferase-P (GST-P) expression in rat liver epithelial cells (228 cells) and a line derived from them (C5 cells) by stable transfection with a metallothionein-activated ras fusion gene (MTrasT24). Earlier studies demonstrated that steady state RNA levels of these genes are increased after transformation of liver cells by MTrasT24 (Proc. Natl. Acad. Sci., 85, 344-348, 1988). In the present study, we found that the rate of gamma GT transcription increased approximately 20 fold after transformation by MTrasT24 while the rate of GST-P transcription increased no more than two fold. However, the stability of GST-P RNA was increased about 3 fold in these cells. Comparisons of gamma GT RNA stability were not possible since nontransformed liver cells (228) contain little or no gamma GT RNA. Thus, the accumulation of gamma GT RNA in C5 cells is heavily dependent on increased rates of transcription while the more modest increases in GST-P RNA levels result in large part from increased RNA stability. In ras transformed cells both transcriptional and post-transcriptional events contribute to the increased steady state RNA levels of cellular genes.