4502

MT2A

MT2;metallothionein 2A;MT2A;metallothionein 2A

MT-2|MT-II|metallothionein-2|metallothionein-2A|metallothionein-II

16q13

protein-coding

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-kappaB signaling. The protein levels of MT2A, IkappaB-alpha and p-IkappaB-alpha (ser32/36) expression were analyzed in a subset of 258 patients by IHC staining. The prognostic effects of MT2A, status of IkappaB-alpha 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 IkappaB-alpha expression (P < 0.001). Furthermore, MT2A was the independent prognostic signature segregated from the status of IkappaB-alpha and pathological features. In addition, MT2A inhibited cell growth through apoptosis and G2/M arrest, which negatively regulated NF-kappaB pathway through up-regulation of IkappaB-alpha and down-regulation of p-IkappaB-alpha and cyclin D1 expression. CONCLUSIONS: MT2A might play a tumor suppressive activity through inhibiting NF-kappaB signaling and may be a prognostic biomarker and potential target for individual therapy of GC patients.