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

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Abstract

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 × 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.

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References

  1. M Abe S Yamashita et al. (2003) ArticleTitleGlobal expression analysis of N-methyl-N′-nitro-N-nitrosoguanidine-induced rat stomach carcinomas using oligonucleotide microarrays. Carcinogenesis 24 861–867 Occurrence Handle10.1093/carcin/bgg030 Occurrence Handle1:CAS:528:DC%2BD3sXkt1WrsLs%3D Occurrence Handle12771029

    Article  CAS  PubMed  Google Scholar 

  2. BN Ames LS Gold (1990) ArticleTitleToo many rodent carcinogens: mitogenesis increases mutagenesis [published erratum appears in Science 1990 Sep 28;249(4976):1487]. Science 249 970–971 Occurrence Handle1:STN:280:By%2BA2s7jtVA%3D Occurrence Handle2136249

    CAS  PubMed  Google Scholar 

  3. NM Bass (1985) ArticleTitleFunction and regulation of hepatic and intestinal fatty acid binding proteins. Chem Phys Lipids 38 95–114 Occurrence Handle10.1016/0009-3084(85)90060-X Occurrence Handle1:CAS:528:DyaL2MXltlOhtbw%3D Occurrence Handle4064226

    Article  CAS  PubMed  Google Scholar 

  4. NM Bass (1988) ArticleTitleThe cellular fatty acid binding proteins: aspects of structure, regulation, and function. Int Rev Cytol 111 143–184 Occurrence Handle1:CAS:528:DyaL1cXmt1Cku70%3D Occurrence Handle3074959

    CAS  PubMed  Google Scholar 

  5. SP Bralow M Gruenstein DR Meranze (1973) ArticleTitleHost resistance to gastric adenocarcinomatosis in three strains of rats ingesting N-methyl-N′-nitro-N-nitrosoguanidine. Oncology 27 168–180 Occurrence Handle1:CAS:528:DyaE3sXktVWitbs%3D Occurrence Handle4701583

    CAS  PubMed  Google Scholar 

  6. SM Cohen LB Ellwein (1990) ArticleTitleCell proliferation in carcinogenesis. Science 249 1007–1011 Occurrence Handle1:CAS:528:DyaK3cXls1Kqtbk%3D Occurrence Handle2204108

    CAS  PubMed  Google Scholar 

  7. D Dong SE Ruuska DJ Levinthal N Noy (1999) ArticleTitleDistinct roles for cellular retinoic acid-binding proteins I and II in regulating signaling by retinoic acid. J Biol Chem 274 23695–23698 Occurrence Handle10.1074/jbc.274.34.23695 Occurrence Handle1:CAS:528:DyaK1MXlsVOns70%3D Occurrence Handle10446126

    Article  CAS  PubMed  Google Scholar 

  8. M Esteller M Guo V Moreno MA Peinado G Capella et al. (2002) ArticleTitleHypermethylation-associated inactivation of the cellular retinol-binding-protein 1 gene in human cancer. Cancer Res 62 5902–5905 Occurrence Handle1:CAS:528:DC%2BD38XotFyktLw%3D Occurrence Handle12384555

    CAS  PubMed  Google Scholar 

  9. K Hayashi H Yokozaki S Goodison N Oue T Suzuki et al. (2001) ArticleTitleInactivation of retinoic acid receptor beta by promoter CpG hypermethylation in gastric cancer. Differentiation 68 13–21 Occurrence Handle10.1046/j.1432-0436.2001.068001013.x Occurrence Handle1:CAS:528:DC%2BD3MXnvVamtbo%3D Occurrence Handle11683489

    Article  CAS  PubMed  Google Scholar 

  10. RM Kaikaus NM Bass RK Ockner (1990) ArticleTitleFunctions of fatty acid binding proteins. Experientia 46 617–630 Occurrence Handle1:CAS:528:DyaK3cXkvFegt7g%3D Occurrence Handle2193826

    CAS  PubMed  Google Scholar 

  11. CD King GR Rios MD Green TR Tephly (2000) ArticleTitleUDP-glucuronosyltransferases. Curr Drug Metab 1 143–161 Occurrence Handle1:CAS:528:DC%2BD3cXntlOrs70%3D Occurrence Handle11465080

    CAS  PubMed  Google Scholar 

  12. DA Miller HF DeLuca (1986) ArticleTitleBiosynthesis of retinoyl-beta-glucuronide, a biologically active metabolite of all-trans-retinoic acid. Arch Biochem Biophys 244 179–186 Occurrence Handle1:CAS:528:DyaL28XmsVeisQ%3D%3D Occurrence Handle3080946

    CAS  PubMed  Google Scholar 

  13. H Ohgaki T Sugimura (1997) Experimental gastric cancer. T Sugimura M Sasako (Eds) Gastric Cancer Oxford University Press New York 73–86

    Google Scholar 

  14. H Ohgaki T Kawachi N Matsukura K Morino M Miyamoto et al. (1983) ArticleTitleGenetic control of susceptibility of rats to gastric carcinoma. Cancer Res 43 3663–3667 Occurrence Handle1:STN:280:BiyB3s3ntlI%3D Occurrence Handle6861136

    CAS  PubMed  Google Scholar 

  15. H Ohgaki M Tomihari S Sato P Kleihues T Sugimura (1988) ArticleTitleDifferential proliferative response of gastric mucosa during carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine in susceptible ACI rats, resistant Buffalo rats, and their hybrid F1 cross. Cancer Res 48 5275–5279 Occurrence Handle1:CAS:528:DyaL1cXlvVGhtb0%3D Occurrence Handle3409251

    CAS  PubMed  Google Scholar 

  16. N Oue J Motoshita H Yokozaki K Hayashi E Tahara et al. (2002) ArticleTitleDistinct promoter hypermethylation of p16INK4a, CDH1, and RAR-beta in intestinal, diffuse-adherent, and diffuse-scattered type gastric carcinomas. J Pathol 198 55–59 Occurrence Handle10.1002/path.1170 Occurrence Handle1:CAS:528:DC%2BD38Xns1Wiurs%3D Occurrence Handle12210063

    Article  CAS  PubMed  Google Scholar 

  17. NS Tan NS Shaw N Vinckenbosch P Liu R Yasmin et al. (2002) ArticleTitleSelective cooperation between fatty acid binding proteins and peroxisome proliferator-activated receptors in regulating transcription. Mol Cell Biol 22 5114–5127 Occurrence Handle10.1128/MCB.22.14.5114-5127.2002 Occurrence Handle1:CAS:528:DC%2BD38XltVOqtrg%3D Occurrence Handle12077340

    Article  CAS  PubMed  Google Scholar 

  18. M Tatematsu T Aoki T Inoue M Mutai C Furihata et al. (1988) ArticleTitleCoefficient induction of pepsinogen 1-decreased pyloric glands and gastric cancers in five different strains of rats treated with N-methyl-N′-nitro-N-nitrosoguanidine. Carcinogenesis 9 495–498 Occurrence Handle1:CAS:528:DyaL1cXktFymu7Y%3D Occurrence Handle3345588

    CAS  PubMed  Google Scholar 

  19. M Tatsuta H Iishi M Baba R Hirasawa H Yano et al. (1999) ArticleTitleAttenuation by all-trans-retinoic acid of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine in Wistar rats. Br J Cancer 79 732–736 Occurrence Handle10.1038/sj.bjc.6690117 Occurrence Handle1:CAS:528:DyaK1MXhslCnsL4%3D Occurrence Handle10070861

    Article  CAS  PubMed  Google Scholar 

  20. HP Vo DL Crowe (1998) ArticleTitleTranscriptional regulation of retinoic acid responsive genes by cellular retinoic acid binding protein-II modulates RA mediated tumor cell proliferation and invasion. Anticancer Res 18 217–224 Occurrence Handle1:CAS:528:DyaK1cXivVajur0%3D Occurrence Handle9568080

    CAS  PubMed  Google Scholar 

  21. K Wiench E Frei P Schroth M Wiessler (1992) ArticleTitle1-C-glucuronidation of N-nitrosodiethylamine and N-nitrosomethyl-n-pentylamine in vivo and in primary hepatocytes from rats pretreated with inducers. Carcinogenesis 13 867–872 Occurrence Handle1:CAS:528:DyaK38Xls1Glu7o%3D Occurrence Handle1587001

    CAS  PubMed  Google Scholar 

  22. S Yamashita K Wakazono T Sugimura T Ushijima (2002) ArticleTitleProfiling and selection of genes differentially expressed in the pylorus of rat strains with different proliferative responses and stomach cancer susceptibility. Carcinogenesis 23 923–928 Occurrence Handle10.1093/carcin/23.6.923 Occurrence Handle1:CAS:528:DC%2BD38Xlt1Kntbk%3D Occurrence Handle12082013

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by Grants-in-Aid for the 2nd-term Comprehensive Cancer Control Strategy and for Cancer Research from the Ministry of Health, Labor and Welfare; and by a grant from the Princess Takamatsu Cancer Research Fund.

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Correspondence to Toshikazu Ushijima.

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Yamashita, S., Nomoto, T., Ohta, T. et al. Differential expression of genes related to levels of mucosal cell proliferation among multiple rat strains by using oligonucleotide microarrays . Mamm Genome 14, 845–852 (2003). https://doi.org/10.1007/s00335-003-2299-3

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  • DOI: https://doi.org/10.1007/s00335-003-2299-3

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