CEP55 contributes to human gastric carcinoma by regulating cell proliferation
CEP55 contributes to human gastric carcinoma by regulating cell proliferation
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CEP55通过调节细胞增殖促进人类胃癌
DOI：
10.1007/s13277-013-1578-1
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发表时间：
2014-05-01
期刊：
影响因子：
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通讯作者：
Xu, Zekuan
中科院分区：
文献类型：
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作者：
Tao, Jinqiu;Zhi, Xiaofei;Xu, Zekuan
中心体蛋白55（CEP 55）是中心体相关蛋白家族中最新发现的成员，参与细胞周期调控。CEP 55存在于多种正常组织和肝癌等肿瘤细胞中，在肿瘤发生中起重要作用。然而，CEP 55在胃癌（GC）发病机制中的作用仍不清楚。采用实时荧光定量PCR检测胃癌组织和胃癌细胞系中CEP 55的mRNA水平，采用Western blot和免疫组化检测胃癌组织中CEP 55的蛋白表达。在体外和体内研究了CEP 55在调节GC细胞系增殖中的作用。CEP 55在人GC中强烈上调，表明CEP 55有助于GC的发生和进展。CEP 55的异位过表达增强了GC细胞的细胞增殖、集落形成和致瘤性，而CEP 55敲低则抑制了这些作用。我们发现CEP 55诱导的细胞转化是由AKT信号通路介导的。CEP 55的过表达增强了AKT的磷酸化，抑制了p21 WAF 1/Cip 1的活性。此外，在CEP 55敲低的细胞中，由于细胞周期停滞在G2/M期，细胞增殖受到抑制。胃癌组织中CEP 55的表达明显高于正常对照组织。有证据表明CEP 55可能成为胃癌治疗的潜在靶点。
Centrosomal protein 55 (CEP55) is the latest found member in the centrosomal relative protein family, which participates in cell-cycle regulation. CEP55 exists in many kinds of normal tissues and tumour cells such as hepatocellular carcinoma, and is important in carcinogenesis. However, the role of CEP55 in the pathogenesis of gastric cancer (GC) remains unclear. The mRNA levels of CEP55 in GC tissues and GC cell lines were examined by quantitative real-time PCR, and the protein expression of CEP55 in GC tissues was detected by Western blot and immunohistochemistry. The role of CEP55 in regulating the proliferation of GC cell lines was investigated both in vitro and in vivo. CEP55 was strongly upregulated in human GC, indicating that CEP55 contributed to carcinogenesis and progression of GC. Ectopic overexpression of CEP55 enhanced the cell proliferation, colony formation, and tumourigenicity of GC cells, whereas CEP55 knockdown inhibited these effects. We discovered that cell transformation induced by CEP55 was mediated by the AKT signalling pathway. Overexpression of CEP55 enhanced the phosphorylation of AKT and inhibited the activity of p21 WAF1/Cip1. In addition, cellular proliferation was suppressed as a result of cell cycle arrest at the G2/M phase in CEP55-knockdown cells. CEP55 expression was elevated in GC compared with normal control tissues. Credible evidence showed that CEP55 can be a potential therapeutic target in GC.