Overexpression of Cullin1 is associated with poor prognosis of patients with gastric cancer
Overexpression of Cullin1 is associated with poor prognosis of patients with gastric cancer
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Cullin1过度表达与胃癌患者不良预后相关
DOI：
10.1016/j.humpath.2010.09.003
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发表时间：
2011-03-01
期刊：
影响因子：
3.3
通讯作者：
Li, Gang
中科院分区：
文献类型：
--
作者：
Bai, Jin;Zhou, Yan;Li, Gang
Cullin 1（Cul 1）是遍在蛋白E3连接酶Skp 1/Cullin 1/Rbx 1/F-box蛋白复合物的支架蛋白，该复合物遍在参与细胞周期进程、信号转导和转录的广泛蛋白质。为了探讨Cullin 1在胃癌发生发展中的作用，我们检测了Cullin 1在胃癌原发组织中的表达，并分析了Cullin 1表达与临床病理变量和患者生存期之间的相关性。我们构建了一个包含792例原发性胃癌组织的组织芯片，并通过免疫组织化学方法评估了肿瘤活检组织中Cullin 1的表达。通过磺酰罗丹明B细胞增殖实验和细胞粘附实验研究了Cullin 1在胃癌细胞增殖和粘附中的作用。Cullin 1过表达与胃癌TNM分期（P = 0.011）、浸润深度（P = 0.035，比较T1-T3与T4）和淋巴结转移（P = 0.036）显著相关。此外，我们发现Cullin 1高表达与胃癌患者的总体生存率和3年生存率较差之间存在强相关性（分别为P = .042和P = .026）。考克斯回归分析显示，Cullin 1表达是预测胃癌患者3年预后的独立预后因素（P = 0.028）。最后，我们发现Cullin 1敲低通过上调p27表达抑制细胞生长，并通过抑制Src家族激酶和粘着斑激酶的表达降低细胞粘附能力。提示Cullin 1可能是判断胃癌淋巴结转移和预后的一个重要指标。(C)2011 Elsevier Inc. All rights reserved.
Cullin1 (Cul1) is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription. To investigate the role of Cullin1 in the development of gastric cancer, we examined the expression of Cullin1 in primary gastric cancer tissues and analyzed the correlation between Cullin 1 expression and clinicopathologic variables and patients survival. We constructed a tissue microarray that includes 792 primary gastric cancer tissues and evaluated the Cullin1 expression by immunohistochemistry in the tumor biopsies. We also studied the role of Cullin1 in gastric cancer cell proliferation and adhesion by performing sulforhodamine B cell proliferation assay and cell attachment assay. The Cullin 1 overexpression was significantly correlated with gastric cancer TNM stage (P = .011), depth of invasion (P = .035, comparing T1-T3 versus T4), and lymph node metastasis (P = .036). Furthermore, we showed a strong correlation between high Cullin1 expression and worse overall and 3-year survival rates in gastric cancer patients (P = .042 and P = .026, respectively). Cox regression analysis revealed that Cullin 1 expression was an independent prognostic factor to predict 3-year patient outcome in gastric cancer (P = .028). Finally, we found that Cullin 1 knockdown inhibits cell growth by up-regulating p27 expression and decreases cell adhesion ability by suppressing the expression of Src family kinases and focal adhesion kinase. Our data indicated that Cullin1 may be an important marker for human gastric cancer lymph node metastasis and prognosis. (C) 2011 Elsevier Inc. All rights reserved.