title: Gastric Carcinogenesis in the miR-222/221 Transgenic Mouse Model.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) regulate various cellular functions, including development, cell proliferation, apoptosis, and tumorigenesis. Different signatures associated with various tissue types, diagnosis, progression, prognosis, staging, and treatment response have been identified by miRNA expression profiling of human tumors. miRNAs function as oncogenes or as tumor suppressors. The relationship between gastric cancer and miRNA garnered attention due to the high incidence of gastric cancer in Asian countries. miR-222/221 expression increases in gastric tumor tissues. The oncogenic effect of miR-222/221 was previously determined in functional studies and xenograft models. In this study, transgenic mice over-expressing miR-222/221 were generated to confirm the effect of miR-222/221 on gastric carcinogenesis.
  
  
  METHODS
  At 6 weeks of age, 65 transgenic mice and 53 wild-type mice were given drinking water containingN-nitroso-N-methylurea (MNU) for 5 alternating weeks to induce gastric cancer. The mice were euthanized at 36 weeks of age and histologic analysis was performed.
  
  
  RESULTS
  Hyperplasia was observed in 3.77% of the wild-type mice and in 18.46% of the transgenic mice (p=0.020). Adenoma was observed in 20.75% of the wild-type mice and 26.15% of the transgenic mice (p=0.522). Carcinoma was observed in 32.08% of the wild-type mice and 41.54% of the transgenic mice (p=0.341). The frequency of hyperplasia, adenoma, and carcinoma was higher in transgenic mice, but the difference was statistically significant only in hyperplasia.
  
  
  CONCLUSIONS
  These results suggest that hyperplasia, a gastric pre-cancerous lesion, is associated with miR-222/221 expression but miR-222/221 expression does not affect tumorigenesis itself.
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Boram
authors.initials: B
authors.lastname: Choi
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
authors.forename: Tae-Su
authors.initials: TS
authors.lastname: Han
authors.affiliation: Center for RNA Research, Institute for Basic Science, Korea School of Biological Sciences, Seoul National University, Seoul, Korea.|Department of Biochemistry, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Young-Kook
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Keun
authors.initials: K
authors.lastname: Hur
authors.affiliation: Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Byeong-Cheol
authors.initials: BC
authors.lastname: Kang
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Woo-Ho
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hyuk-Joon
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Center for RNA Research, Institute for Basic Science, Korea School of Biological Sciences, Seoul National University, Seoul, Korea.
authors.forename: V Narry
authors.initials: VN
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Han-Kwang
authors.initials: HK
authors.lastname: Yang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D002273:Carcinogens / Q000008:administration & dosage; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics*; D004195:Disease Models, Animal; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D010641:Phenotype; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; C546122:MIRN221 microRNA, mouse; C546123:MIRN222 microRNA, mouse; D035683:MicroRNAs
keywords: Gastric carcinogenesis; MNU (N-nitroso-N-methylurea); Stomach neoplasms; Transgenic mouse; microRNAs