Gene expression analysis of urethane-induced lung tumors in ras H2 mice.

In our previous study, microarray analysis was performed on N-ethyl-N-nitrosourea (ENU)-induced forestomach tumors in transgenic mice carrying the human prototype c-Ha-ras gene (ras H2 mice). Ras-MAPK related genes, including the transgene and mouse endogenous ras genes, that are involved in enhanced carcinogenesis were up-regulated in these tumors. In the present study, ras H2 mice received five intraperitoneal injections of 1,000 mg/kg urethane at 2-day intervals. Subsequently, microarray and RT-PCR analyses for the transgene and some molecules involved in the Ras pathway were performed on the induced lung tumors. In the microarray analysis, gene expression profiles of normal lungs and adenomas showed a distinct pattern, and several genes related to the cell cycle and nucleotide metabolism were up-regulated in the adenomas. RT-PCR confirmed the overexpression of the transgene in lung tumors; however, the up-regulation of the mouse endogenous ras genes was not observed. Some genes showed a similar expression pattern in both ENU- and urethane-induced tumors. These results suggest that the overexpression of the transgene plays an important role in the carcinogenesis of both ENU- and urethane-induced tumors in ras H2 mice. The genes that showed a similar expression pattern in both tumors were considered to be the candidate genes responsible for enhanced carcinogenesis.