Differential expression of genes related to levels of mucosal cell proliferation among multiple rat strains by using oligonucleotide microarrays.

Induction levels of cell proliferation, in response to gastric mucosal damage by N-methyl- N'-nitro- N-nitrosoguanidine (MNNG), are different among rat strains and correlate with susceptibility to MNNG-induced gastric carcinogenesis. Here, we used oligonucleotide microarrays to search for genes that show expression levels accordant with the extents of cell proliferation among six rat strains. Expression levels of 8,800 probe sets were analyzed in the pylorus of ACI, LEW, WKY (strains with strong cell proliferation), F344, (ACI x BUF)F1, and BUF rats (strains with weak cell proliferation) after 2-week MNNG treatment. No genes showed complete accordance, and 22 genes showed accordance with one or two exceptions. After confirmation by quantitative RT-PCR, four genes--cellular retinoic acid-binding protein II ( Crabp2), fatty acid binding protein 1 ( Fabp1), progastricsin (pepsinogen C, Pgc), and UDP-glucuronosyltransferase 2 family member 5 ( Ugt2b5)--were found to show good accordance with only one exception. Crabp2, Fabp1, and Ugt2b5 were differentially expressed between ACI and BUF rats both before and after MNNG treatment. Although Crabp2 had been identified as one of the 16 genes differentially expressed between ACI and BUF rats with cDNA-RDA, Fabp1 and Ugt2b5 were newly identified in this study. All three genes are known to be involved in retinoic acid-mediated signaling and could be involved in the control of differential induction of cell proliferation.