title: Constitutive expression of PPARγ inhibits proliferation and migration of gastric cancer cells and down-regulates Wnt/β-Catenin signaling pathway downstream target genes TERT and ENAH.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the PPAR nuclear hormone receptor superfamily, which plays a crucial role in carcinogenesis. Wnt/β-Catenin signaling pathway has been well certified to contribute to the progression of gastric malignancies. β-Catenin mediates transcriptional regulation by forming a complex with LEF/TCF transcription factors, resulting in activation of downstream target genes such as TERT, ENAH. In this study, we aimed at detecting the effect of PPARγ on TERT, ENAH and explaining the further mechanisms of PPARγ on tumor suppression.
  
  
  METHODS
  The pEGFP-N1-PPARγ recombinant plasmid has already been constructed by researchers in our laboratory. We stably transfected it into three gastric cancer (GC) cell lines (MKN-28, SGC-7901 and BGC-823). CCK-8 and transwell assay were employed to analyze the capability of cell proliferation and metastasis. The mRNA and protein levels were evaluated by real-time PCR and western blot analysis.
  
  
  RESULTS
  After transfected with PPARγ overexpression plasmid, the ability of cell proliferation and migration declined significantly (p<0.05). The expression of PPARγ increased (p<0.05) and β-Catenin was inhibited obviously (p<0.05) in the group of pEGFP-N1-PPARγ plasmid transfection. Meanwhile, the mRNA or protein levels of TERT and ENAH were suppressed (p<0.05) in pEGFP-N1-PPARγ plasmid transfection group compared with control groups.
  
  
  CONCLUSIONS
  PPARγ might inhibit the proliferation and migration of GC cell lines through suppressing the expression of TERT and ENAH. PPARγ played an important role as a physiological regulator and might be a target for the treatment of GC.
authors.affiliation: Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.affiliation: Teaching Center for Preventive Medicine Experiments, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, PR China.
authors.forename: Xiyun
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, PR China.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, PR China.
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, PR China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Nutrition and Food Hygiene, Harbin Medical University, Harbin, Heilongjiang Province, PR China.
authors.forename: Fanyu
authors.initials: F
authors.lastname: Meng
authors.affiliation: Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, PR China. Electronic address: twj8267@sina.com.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Tian
authors.affiliation: Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province, PR China. Electronic address: zhao_yashuang@263.net.
authors.forename: Yashuang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics*; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D013274:Stomach Neoplasms / Q000473:pathology*; D019098:Telomerase / Q000235:genetics*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C511939:Enah protein, human; D008840:Microfilament Proteins; D047495:PPAR gamma; D051153:Wnt Proteins; D051176:beta Catenin; C509186:TERT protein, human; D019098:Telomerase
keywords: ENAH; Gastric cancer; PPARγ; TERT; Wnt/β-Catenin