Journal of Translational Medicine | |
Metallothionein 2A inhibits NF-κB pathway activation and predicts clinical outcome segregated with TNM stage in gastric cancer patients following radical resection | |
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 |
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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.
【 预 览 】
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