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.