Significance of Jab1 Expression in Human Esophageal Squamous Cell Carcinoma
Significance of Jab1 Expression in Human Esophageal Squamous Cell Carcinoma
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DOI：
10.1097/mcg.0b013e3181919245
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发表时间：
2009-07-01
影响因子：
2.9
通讯作者：
Shen, Aiguo
中科院分区：
文献类型：
--
作者：
Wang, Feng;Wang, Yuchan;Shen, Aiguo
目的：检测Jun激活域结合蛋白1和p27在较大系列的食管鳞癌中的表达，并探讨其临床病理意义。背景：p27的低表达与包括食管鳞癌在内的大多数人类肿瘤的预后不良有关。Jab1是AP-1转录因子的共激活因子，通过降解p27蛋白参与Turner进展。研究：对90例食管鳞癌和ECA109细胞进行免疫组织化学和Western印迹分析。采用Kaplan-Meier法进行生存分析。结果：免疫组织化学分析显示，Jab1的表达与p27水平呈负相关，与不良的临床病理变量显著相关。在ECA109细胞中过表达Jab1导致p27水平下降，这种下降对26S蛋白酶体抑制剂敏感。亚细胞分离证实Jab1可以导致p27的核输出。生存分析显示，JAB1过表达与总生存期显著相关(P<；0.001)。当Jab1和p27联合表达时，Jab1(+)/p27(-)患者的总生存期较差(P<；0.001)，且Jab1(+)/淋巴结(+)患者的无瘤生存期和总生存期(P<；0.001)明显低于其他表型患者(P<；0.001)。
Goal: The aim of the present study was to examine the expression of Jun activation domain-binding protein 1(Jab1) and p27 and to elucidate its clinicopathologic significance in a larger series of squamous cell carcinoma (SCC) of the esophagus.Background: Reduced expression of p27 has been associated with poor prognosis in most human cancers, including esophageal SCCs. Jab1 is known as a coactivator of AP-1 transcription factor, which contributes to turner progression by degrading the p27 protein.Study: Immunohistochemical and Western blot analysis were performed in 90 cases of esophageal SCCs and ECA109 cells. Survival analyses were performed by using the Kaplan-Meier method.Results: Immunohistochemical analysis showed that Jab1 expression was negatively associated with p27 level and significantly associated with unfavorable clinicopathologic variables. Overexpression of Jab1 in ECA109 cells resulted in decreased p27 level and this decrease was sensitive to 26S proteasome inhibitors. Subcellular fractionation confirmed Jab1 could lead to nuclear export of p27. Survival analysis revealed that Jab1 overexpression was significantly associated with overall survival (P < 0.001). When Jab1 and p27 are combined, patients with Jab1(+)/p27(-) revealed poorer overall Survival (P < 0.001), what's more, patients with the phenotype of Jab1(+)/lymph node(+) had poorer disease-free and overall survival than others (P < 0.001).Conclusions: These findings suggest that Jab1 is involved in the pathogenesis of esophageal SCC and that elevated levels of Jab1 expression may indicate a poor prognosis for patients with esophageal SCC.