title: MTA2 promotes gastric cancer cells invasion and is transcriptionally regulated by Sp1.
abstract: BACKGROUND
  MTA2 gene belongs to metastasis associated family, and is highly expressed in some solid tumors, including gastric cancer. Its biological function in gastric cancer is currently undefined.
  
  
  METHODS
  Metastasis-associated tumor gene family 2 (MTA2) and transcription factor specificity protein 1 (Sp1) expression were detected in 127 gastric cancer samples by immunohistochemistry staining. SGC-7901 and AGS gastric cancer cell lines transfected by MTA2 shRNA was used for biological function investigation. Binding and regulation activities of Sp1 on MTA2 promoter were investigated by chromatin immunoprecipitation and luciferase reporter gene.
  
  
  RESULTS
  The expression rate of MTA2 in gastric cancer tissues was 55.9% (71/127), and its expression was closely related to the depth of tumor invasion, lymph nodes metastasis, and TNM staging. MTA2 knockdown in human SGC-7901 and AGS gastric cancer cells significantly inhibited migration and invasion in vitro, and disrupted structure of cytoskeleton. MTA2 knockdown also attenuated xenografts growth and lung metastasis in nude mice model. MTA2 expression was positively correlated with transcription factor Sp1 in gastric cancer tissues (r = 0.326, P < 0.001). Sp1 bound to human MTA2 gene promoter at region from -1043 bp to -843 bp. Transcriptional activity of MTA2 promoter could be enhanced by Sp1 overexpression.
  
  
  CONCLUSIONS
  MTA2 knockdown impairs invasion and metastasis of gastric cancer cells, and attenuates xenografts growth in vivo. Sp1 regulates MTA2 expression at transcriptional level.
authors.affiliation: Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No, 197 Ruijin er Road, Shanghai 200025, P,R, China. jun_zj10977@163.com.
authors.forename: Chenfei
authors.initials: C
authors.lastname: Zhou
authors.forename: Jun
authors.initials: J
authors.lastname: Ji
authors.forename: Qu
authors.initials: Q
authors.lastname: Cai
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.forename: Xuehua
authors.initials: X
authors.lastname: Chen
authors.forename: Yingyan
authors.initials: Y
authors.lastname: Yu
authors.forename: Bingya
authors.initials: B
authors.lastname: Liu
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhu
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000502:physiology*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D014158:Transcription, Genetic
chemical_list: D012097:Repressor Proteins; D016329:Sp1 Transcription Factor; C120917:MTA2 protein, human; D006655:Histone Deacetylases