Metallothionein 2A inhibits NF-κB pathway activation and predicts clinical outcome segregated with TNM stage in gastric cancer patients following radical resection

Journal of Translational Medicine

Youyong Lu¹  Jun Yu²  Wenmei Li¹  Jiantao Cui¹  Xin Yin¹  Rui Xing¹  Jiaqiang Huang³  Yuanming Pan¹ 

[1] Laboratory of Molecular Oncology, Key laboratory of Carcinogenesis and Translational Research, Ministry of Education, Peking University Cancer Hospital & Institute, No.52 Fucheng Road, Beijing, Haidian District 100142, People's Republic of China;Institute of Digestive Disease and Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, SAR, China;College of Life Sciences & Bioengineering, School of Science, Beijing Jiaotong University, No.3 ShangyuanCun, Beijing, Haidian District 100044, People's Republic of China

关键词: TNM stage;    Prognosis;    Gastric cancer;    NF-κB signaling;    Metallothionein 2A;   

Others  :  827129
DOI  :  10.1186/1479-5876-11-173

 received in 2013-03-17, accepted in 2013-07-10,  发布年份 2013

【 摘 要 】

Background

Metallothionein 2A (MT2A) as a stress protein, plays a protective role in gastric mucosal barrier. Its role in the development of gastric cancer (GC) is unclear. The mechanism of MT2A will be investigated in gastric tumorigenesis.

Methods

MT2A expression was detected in 973 gastric specimens. The biological function was determined through ectopic expressing MT2A in vitro and in vivo. The possible downstream effectors of MT2A were investigated in NF-κB signaling. The protein levels of MT2A, IκB-α and p-IκB-α (ser32/36) expression were analyzed in a subset of 258 patients by IHC staining. The prognostic effects of MT2A, status of IκB-α and TNM stage were evaluated using the Kaplan-Meier method and compared using the log-rank test.

Results

Decreased MT2A expression was detected in cell lines and primary tumors of GC. In clinical data, loss of MT2A (MT2A + in Normal (n =171, 76.0%); Intestinal metaplasia (n = 118, 50.8%); GC (n = 684. 22.4%, P < 0.001)) was associated with poor prognosis (P < 0.001), advanced TNM stage (P = 0.05), and down-regulation of IκB-α expression (P < 0.001). Furthermore, MT2A was the independent prognostic signature segregated from the status of IκB-α and pathological features. In addition, MT2A inhibited cell growth through apoptosis and G2/M arrest, which negatively regulated NF-κB pathway through up-regulation of IκB-α and down-regulation of p-IκB-α and cyclin D1 expression.

Conclusions

MT2A might play a tumor suppressive activity through inhibiting NF-κB signaling and may be a prognostic biomarker and potential target for individual therapy of GC patients.

【 授权许可】

   
2013 Pan et al.; licensee BioMed Central Ltd.

【 图 表 】

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