title: PDCD2 and NCoR1 as putative tumor suppressors in gastric gastrointestinal stromal tumors.
abstract: OBJECTIVE
  Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract. Previously, PDCD2 (programmed cell death protein 2) has been identified as a putative tumor suppressor in gastric cancer. As yet, however, no reports on PDCD2 expression and its physical interactor NCoR1 (nuclear receptor co-repressor), and their effects in GIST have been reported.
  
  
  METHODS
  The expression of PDCD2 and NCoR1 was assessed in 43 primary gastric GIST and normal gastric tissue samples using Western blotting and quantitative real-time PCR. Next, associations between PDCD2 and NCoR1 expression and various clinicopathological features, including survival, were determined. To assess the effects of PDCD2 and NCoR1 expression in vitro, two GIST-derived cell lines (GIST-T1 and GIST882) were (co-)transfected with the expression vectors pEGFP-N1-PDCD2 and pcDNA3.1-NCoR1, after which the cells were subjected to CCK-8, PI staining and Annexin V-FITC/PI double staining assays, respectively. Finally, the mechanisms of action of PDCD2 and NCoR1 in GIST-derived cells were determined using immunoprecipitation and Western blotting assays.
  
  
  RESULTS
  We found that the PDCD2 and NCoR1 protein levels were lower in gastric GIST tissues than in normal gastric tissues. The PDCD2 and NCoR1 expression levels were found to be significantly associated with the survival of the patients. Through exogenous expression analyses, we found that PDCD2 and NCoR1 can decrease proliferation, and increase apoptosis and G1 cell cycle arrest, in GIST-derived cells. Furthermore, we found that PDCD2 and NCoR1 can activate Smad2 and Smad3.
  
  
  CONCLUSIONS
  Our data indicate that both PDCD2 and NCoR1 may act as tumor suppressors in GIST cells through the Smad signaling pathway.
authors.affiliation: Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, 110122, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, 110122, People's Republic of China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Song
authors.affiliation: Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.
authors.forename: Xian-Min
authors.initials: XM
authors.lastname: Bu
authors.affiliation: Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, 110122, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, 110122, People's Republic of China. cmu_chenghai@163.com.
authors.forename: Cheng-Hai
authors.initials: CH
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D056971:Nuclear Receptor Co-Repressor 1 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C539127:NCOR1 protein, human; D056971:Nuclear Receptor Co-Repressor 1; C094601:PDCD2 protein, human; D012333:RNA, Messenger; D051785:Smad Proteins; D025521:Tumor Suppressor Proteins
keywords: GIST; NCoR1; PDCD2; Smad; Survival rate