title: The transcription factor FOXA2 suppresses gastric tumorigenesis in vitro and in vivo.
abstract: OBJECTIVE
  The transcription factor forkhead box A2 (FOXA2) plays a central role in the development of endoderm-derived organs. It has been reported that FOXA2 acts as a suppressor in many kinds of tumor. However, little is known about the role of FOXA2 in gastric cancer.
  
  
  METHODS
  The expression of FOXA2 in gastric cancer tissue samples from 89 patients was assessed by immunohistochemistry, and the clinicopathological characteristics of the samples were analyzed. The human gastric cancer cell line, BGC-823, was used to investigate the effects of FOXA2 in gastric cancer in vitro and in vivo and the potential mechanism involved was explored.
  
  
  RESULTS
  FOXA2 expression in human gastric cancer cell lines and human gastric cancer tissues was lower compared with the normal gastric epithelium cell line GES1 and normal adult gastric tissues, respectively. Patients with high FOXA2 expression level had longer 5-year overall survival than those with low FOXA2 expression level. FOXA2 markedly inhibited growth of BGC-823 cells accompanied with the cell cycle arrest and apoptosis. Infection of BGC-823 cells by FOXA2 lentivirus resulted in reduced cell tumorigenesis in vitro and in vivo. Moreover, expression of Mucin 5AC was up-regulated along with increased expression of exogenous FOXA2 in BGC-823 cells; in contrast, dedifferentiation markers, BMI, CD54 and CD24, were down-regulated.
  
  
  CONCLUSIONS
  These results suggest that FOXA2 induces the differentiation of gastric cancer and highlight FOXA2 as a novel therapeutic target and prognostic marker for human gastric cancer.
authors.affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China.
authors.forename: Chang-Peng
authors.initials: CP
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Shi
authors.forename: Ping-Fang
authors.initials: PF
authors.lastname: Hu
authors.forename: Bei-Fang
authors.initials: BF
authors.lastname: Ning
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Wan-Sheng
authors.initials: WS
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Wei-Fen
authors.initials: WF
authors.lastname: Xie
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D063646:Carcinogenesis; D059447:Cell Cycle Checkpoints / Q000502:physiology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D051542:Hepatocyte Nuclear Factor 3-beta / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D055271:Mucin 5AC / Q000378:metabolism; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
chemical_list: C496502:FOXA2 protein, human; D055271:Mucin 5AC; D051542:Hepatocyte Nuclear Factor 3-beta