TGM3, a candidate tumor suppressor gene, contributes to human head and neck cancer

Molecular Cancer

Research

Jianjun Zhang¹  Wantao Chen¹  Xiangbing Wu¹  Xu Wang¹  Wei Cao¹  Zhongjing Lv¹  Xing Qin¹  Yadi Wu² 

[1] 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, 200011, Shanghai, China;Shanghai Research Institute of Stomatology and Shanghai Key Laboratory of Stomatology, 200011, Shanghai, China;Shanghai Research Institute of Stomatology and Shanghai Key Laboratory of Stomatology, 200011, Shanghai, China;

关键词: Transglutaminase 3;    Head and neck cancer;    Tumor suppressor;    Methylation;    Prognostic predictor;   

DOI  :  10.1186/1476-4598-12-151

 received in 2013-08-02, accepted in 2013-11-25,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundIn 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.MethodsThe 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.ResultsTGM3 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.ConclusionsThe 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.

【 授权许可】

Unknown   
© Wu et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.