title: Effect of adenovirus-mediated PTEN gene on ulcerative colitis-associated colorectal cancer.
abstract: OBJECTIVE
  This study investigated the expression pattern of PTEN and its effect on carcinogenesis of ulcerative colitis-associated colorectal cancer, leading to insights into the underlying molecular mechanism.
  
  
  METHODS
  We established a mouse model of ulcerative colitis-associated colorectal cancer by treating the animals with azoxymethane (AOM) and dextran sulphate sodium (DSS), and investigated the inflammation-dysplasia-carcinoma sequence. Expression patterns of PTEN, p-Akt and Ki-67 were shown by immunohistochemistry; western blotting techniques were used to detect protein expression of PTEN, p-Akt and caspase 3; TUNEL assay was used to measure apoptosis in colon epithelial cells; and colorimetric analysis was able to determine MPO activity in colon tissues.
  
  
  RESULTS
  During the inflammation-dysplasia-carcinoma sequence, PTEN expression gradually decreased, while p-Akt expression increased; PTEN and p-Akt levels were negatively correlated. Compared to the AOM-DSS and Ad-0 groups, Ad-PTEN mice had longer colons, fewer tumours (P < 0.01) and smaller tumour sizes (P < 0.05). After injecting Ad-PTEN, expression of p-Akt, Ki-67 and MPO activity decreased dramatically, whereas PTEN increased. The TUNEL assay showed increased apoptotic cells and caspase 3 expression in the Ad-PTEN group.
  
  
  CONCLUSIONS
  PTEN plays an important role in the inflammation-dysplasia-carcinoma sequence and may be a new molecular target in preventing and treating ulcerative colitis-associated colorectal cancer.
authors.affiliation: Department of Gastroenterology and Geriatrics Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Gong Xiang
authors.initials: GX
authors.lastname: Liu
authors.forename: Yu Lan
authors.initials: YL
authors.lastname: Liu
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Xiao Li
authors.initials: XL
authors.lastname: Huang
authors.forename: Hua Tian
authors.initials: HT
authors.lastname: Gan
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D049109:Cell Proliferation; D003093:Colitis, Ulcerative / Q000150:complications* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D003106:Colon / Q000201:enzymology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000150:complications* / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D015316:Genetic Therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D009195:Peroxidase; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase