Yamashita Satoshi, Nomoto Tomoko, Ohta Tsutomu, Ohki Misao, Sugimura Takashi, Ushijima Toshikazu
Carcinogenesis Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Mamm Genome. 2003 Dec;14(12):845-52. doi: 10.1007/s00335-003-2299-3.
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.
N-甲基-N'-硝基-N-亚硝基胍（MNNG）对胃黏膜造成损伤后，不同大鼠品系的细胞增殖诱导水平存在差异，且与MNNG诱导胃癌发生的易感性相关。在此，我们使用寡核苷酸微阵列来寻找在六种大鼠品系中表达水平与细胞增殖程度相符的基因。在接受为期2周的MNNG处理后，对ACI、LEW、WKY（细胞增殖强烈的品系）、F344、（ACI×BUF）F1和BUF大鼠（细胞增殖较弱的品系）幽门中的8800个探针集的表达水平进行了分析。没有基因表现出完全一致，有22个基因表现出有一两个例外的一致性。经定量逆转录-聚合酶链反应（RT-PCR）确认后，发现四个基因——细胞视黄酸结合蛋白II（Crabp2）、脂肪酸结合蛋白1（Fabp1）、前胃蛋白酶原（胃蛋白酶原C，Pgc）和UDP-葡萄糖醛酸基转移酶2家族成员5（Ugt2b5）——仅存在一个例外的良好一致性。在MNNG处理前后，Crabp2、Fabp1和Ugt2b5在ACI和BUF大鼠之间均存在差异表达。虽然Crabp2已被鉴定为通过cDNA代表性差异分析在ACI和BUF大鼠之间差异表达的16个基因之一，但Fabp1和Ugt2b5是在本研究中首次鉴定出来的。已知这三个基因均参与视黄酸介导的信号传导，可能参与细胞增殖差异诱导的调控。
