Han Fei, Zhang Long, Qiu Weizhe, Yi Xianghua
Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China.
Pathol Res Pract. 2016 Jan;212(1):31-7. doi: 10.1016/j.prp.2015.11.005. Epub 2015 Nov 10.
This study investigated the relationships of TRAF6 expression with clinical pathologic parameters and the prognosis of patients with gastric cancer. This study also explored the roles of TRAF6 in cell apoptosis and invasiveness, as well as underlying molecular mechanism of gastric cancer cell line in vitro.
A total of 90 cases of tissue microarrays were immunohistochemically analyzed for TRAF6 expression. Cell proliferation was measured by MTT assay. Flow cytometry was used for analyzing cell apoptosis and cell invasion ability was detected by a Transwell invasion assay. Protein expression was assessed by Western blotting.
TRAF6 was expressed in 53 of 90 (58.9%) cases of gastric cancer. TRAF6 expression was significantly positively correlated with advanced N stage, pathological stage and a poor prognosis, but not an independent predictor of a poor prognosis in gastric cancer (p=0.083). The knockdown of TRAF6 increased cell apoptosis and reduced invasive ability of BGC-823 cell. Moreover, TRAF6 down-regulation decreased protein levels of phosphor-Akt, Bcl-2 and MMP9 and up-regulation of Bax in BGC-823 cell. Inversely, overexpression of TRAF6 in SGC-7901 cells increased protein levels of phosphor-Akt, Bcl-2 and MMP9 and down-regulation of Bax.
The expression of TRAF6 was positively correlated with an advanced N stage and acted as a predictor of a poor prognosis in patients with gastric cancer. Moreover, TRAF6 regulating cell apoptosis and invasive ability of gastric cancer cells might be associated with Akt activation and alterations of protein expression of Bcl2, Bax and MMP9.
本研究调查了TRAF6表达与胃癌患者临床病理参数及预后的关系。本研究还探讨了TRAF6在细胞凋亡和侵袭中的作用，以及体外胃癌细胞系的潜在分子机制。
对90例组织芯片进行免疫组织化学分析，检测TRAF6表达。采用MTT法检测细胞增殖。通过流式细胞术分析细胞凋亡，采用Transwell侵袭试验检测细胞侵袭能力。通过蛋白质印迹法评估蛋白质表达。
90例胃癌患者中53例（58.9%）表达TRAF6。TRAF6表达与N分期晚、病理分期及预后不良显著正相关，但不是胃癌预后不良的独立预测因素（p=0.083）。敲低TRAF6可增加BGC-823细胞的凋亡并降低其侵袭能力。此外，下调TRAF6可降低BGC-823细胞中磷酸化Akt、Bcl-2和MMP9的蛋白水平，并上调Bax。相反，在SGC-7901细胞中过表达TRAF6可增加磷酸化Akt、Bcl-2和MMP9的蛋白水平，并下调Bax。
TRAF6的表达与N分期晚呈正相关，可作为胃癌患者预后不良的预测指标。此外，TRAF6调节胃癌细胞的凋亡和侵袭能力可能与Akt激活以及Bcl2、Bax和MMP9蛋白表达的改变有关。
