title: TGM3, a candidate tumor suppressor gene, contributes to human head and neck cancer.
abstract: BACKGROUND
  In our previous study using oligonucleotide microarrays, we revealed that transglutaminase 3 (TGM3) was remarkably down-regulated in head and neck cancer (HNC). However, the potential of TGM3 as a useful biomarker or molecular target for HNC is unclear.
  
  
  METHODS
  The transcriptional and post-translational status of TGM3 in HNC cell lines and specimens was detected using real-time PCR and western blot analysis. Bisulfate-treated DNA sequencing was used to analyze the molecular mechanism of TGM3 gene silencing. In addition, the effects of TGM3 on the proliferation, colony formation and induction of apoptosis in vitro and tumorigenicity in vivo were investigated through exogenous expression of TGM3 in HNC cells. Immunohistochemistry was used to evaluate TGM3 expression in large HNC samples.
  
  
  RESULTS
  TGM3 was down-regulated in HNC samples and cell lines (P < 0.0001). The hypermethylation of a promoter CpG island was one of the mechanisms of silencing the TGM3 gene in HNC. Exogenous expression of TGM3 in HNC cells could inhibit the proliferation and enhance the apoptosis of HNC cells in vitro and suppress tumor growth in vivo. In addition, TGM3 protein levels were strongly associated with the pathological differentiation of HNC tissues (P = 0.0037). Survival analysis revealed that low TGM3 expression was associated with worse overall survival (P = 0.0002), and TGM3 expression level was an independent predictor in patients with HNC.
  
  
  CONCLUSIONS
  The studies prove that TGM3, as a candidate tumor suppressor, contributes to the carcinogenesis and development of HNC and may serve as a useful biomarker for patients with HNC.
authors.affiliation: Department of Oral and Maxillofacial-Head and Neck Oncology and Facuty of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. chenwantao2002@hotmail.com.
authors.forename: Xiangbing
authors.initials: X
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhongjing
authors.initials: Z
authors.lastname: Lv
authors.forename: Xing
authors.initials: X
authors.lastname: Qin
authors.forename: Yadi
authors.initials: Y
authors.lastname: Wu
authors.forename: Wantao
authors.initials: W
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000556:secondary; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D004794:Enzyme Repression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009368:Neoplasm Transplantation; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011503:Transglutaminases / Q000235:genetics*; D047368:Tumor Burden
chemical_list: D012333:RNA, Messenger; C498712:TGM3 protein, human; D011503:Transglutaminases