Study of control mechanisms of gene expression related to colorectal cancer by intestinal flora in rasH2 mice

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1. RasH2 mice harboring human prototype c-Ha-ras genes were injected with 1,2-dimethylhydrazine and examined for mutation and expression levels of human c-Ha-ras, murine Ki-ras, Na-ras and p53. There were no point mutations in these genes. The expression level of transgene mRNA determined by real time RT-PCR was shown to be higher in tumors than in non-tumor colorectal tissues, and expression levels by RT-PCR of murine Ki-ras, Na-ras and p53 in the tumors were no different from those in the non-tumor colorectal tissues.2. Expression levels of cancer related genes in the tumors and the non-tumor tissues of rasH2 and non-Tg mice were compared using Gene Navigator^<TM> cDNA Array System (TOYOBO). For 11 genes, MMP7, Clusterin, nm23, c-jun, SLC, Bad, Bax, Gelsolin, Ran, SkpI, and p19, expression levels were higher in the tumors than in the non-tumor colorectal tissues in both rasH2 and non-Tg mice.3. To confirm the high expression levels of 11 genes mentioned above, RT-PCR analysis was performed. Only. MMP7 and Clusterin genes were expressed more in the tumors than in the non-tumor tissues in both rasH2 and non-Tg mice.4. Expression levels of cancer related genes between tumors and non-tumor tissues in rasH2 mice were similar to those in non-Tg mice.